CORD-19-Sentences  

CORD-19:a80bc93a9b4851d9f4925885f9436f3739781333 JSONTXT 9 Projects

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Id Subject Object Predicate Lexical cue
TextSentencer_T1 0-18 Sentence denotes The Golgi Complex:
T50708 0-18 Sentence denotes The Golgi Complex:
TextSentencer_T2 19-36 Sentence denotes In Vitro Veritas?
T97997 19-36 Sentence denotes In Vitro Veritas?
TextSentencer_T3 37-43 Sentence denotes Review
T69947 37-43 Sentence denotes Review
TextSentencer_T4 45-53 Sentence denotes Abstract
T77356 45-53 Sentence denotes Abstract
TextSentencer_T5 54-185 Sentence denotes Understanding thestructure and function of theGolgi comiplex has proved to be among the more challenging probllems in cell biology.
T94812 54-185 Sentence denotes Understanding thestructure and function of theGolgi comiplex has proved to be among the more challenging probllems in cell biology.
TextSentencer_T6 186-349 Sentence denotes The last several years have turned out Ito be particularly exciting in this respect since they have Iyielded new insights and ideas at an increasingly rapid ipace.
T57730 186-349 Sentence denotes The last several years have turned out Ito be particularly exciting in this respect since they have Iyielded new insights and ideas at an increasingly rapid ipace.
TextSentencer_T7 350-532 Sentence denotes This period of advance has largely been due to the Idevelopment of powerful new biochemical, morphological, #and genetic approaches to unraveling the complexities of 'this organelle.
T72439 350-532 Sentence denotes This period of advance has largely been due to the Idevelopment of powerful new biochemical, morphological, #and genetic approaches to unraveling the complexities of 'this organelle.
TextSentencer_T8 533-634 Sentence denotes While much remains to be discovered, the Iproblem now is how to integrate this wealth of information.
T58476 533-634 Sentence denotes While much remains to be discovered, the Iproblem now is how to integrate this wealth of information.
TextSentencer_T9 635-808 Sentence denotes 'To see if this is possible, we will first summarize how the lslolgi is commonly believed to work and then evaluate the lstrength of the evidence that underlies these views.
T26175 635-808 Sentence denotes 'To see if this is possible, we will first summarize how the lslolgi is commonly believed to work and then evaluate the lstrength of the evidence that underlies these views.
TextSentencer_T10 810-886 Sentence denotes iplex has proved to be among the more challenging probllems in cell biology.
T77788 810-886 Sentence denotes iplex has proved to be among the more challenging probllems in cell biology.
TextSentencer_T11 887-1050 Sentence denotes The last several years have turned out Ito be particularly exciting in this respect since they have Iyielded new insights and ideas at an increasingly rapid ipace.
T15088 887-1050 Sentence denotes The last several years have turned out Ito be particularly exciting in this respect since they have Iyielded new insights and ideas at an increasingly rapid ipace.
TextSentencer_T12 1051-1233 Sentence denotes This period of advance has largely been due to the Idevelopment of powerful new biochemical, morphological, #and genetic approaches to unraveling the complexities of 'this organelle.
T8269 1051-1233 Sentence denotes This period of advance has largely been due to the Idevelopment of powerful new biochemical, morphological, #and genetic approaches to unraveling the complexities of 'this organelle.
TextSentencer_T13 1234-1335 Sentence denotes While much remains to be discovered, the Iproblem now is how to integrate this wealth of information.
T28897 1234-1335 Sentence denotes While much remains to be discovered, the Iproblem now is how to integrate this wealth of information.
TextSentencer_T14 1336-1509 Sentence denotes 'To see if this is possible, we will first summarize how the lslolgi is commonly believed to work and then evaluate the lstrength of the evidence that underlies these views.
T1624 1336-1509 Sentence denotes 'To see if this is possible, we will first summarize how the lslolgi is commonly believed to work and then evaluate the lstrength of the evidence that underlies these views.
TextSentencer_T15 1510-1593 Sentence denotes Present View of the Golgi 'The Golgi complex is essentially a carbohydrate factory.
T88287 1510-1593 Sentence denotes Present View of the Golgi 'The Golgi complex is essentially a carbohydrate factory.
TextSentencer_T16 1594-1728 Sentence denotes In <animal cells, it is engaged in the biosynthesisof glycolipids (and of oligosaccharide portions of glycoproteins and proteoglycans.
T60095 1594-1728 Sentence denotes In <animal cells, it is engaged in the biosynthesisof glycolipids (and of oligosaccharide portions of glycoproteins and proteoglycans.
TextSentencer_T17 1729-1831 Sentence denotes In plant cells, it has the additional task of producing a wide range of extracellular polysaccharides.
T17992 1729-1831 Sentence denotes In plant cells, it has the additional task of producing a wide range of extracellular polysaccharides.
TextSentencer_T18 1832-2108 Sentence denotes The factory receives its substrates for glycosylation from the iendoplasmic reticulum (ER), transports its raw materials (monosaccharide precursors) in from the cytosol, and dis-,tributes its completed protein, lipid, and polysaccharide Iproducts to a variety of destinations.
T82523 1832-2108 Sentence denotes The factory receives its substrates for glycosylation from the iendoplasmic reticulum (ER), transports its raw materials (monosaccharide precursors) in from the cytosol, and dis-,tributes its completed protein, lipid, and polysaccharide Iproducts to a variety of destinations.
TextSentencer_T19 2109-2229 Sentence denotes 'Transport through the Golgi Is Directional (One of the most compelling features of the Golgi complex ,IS its structure.
T89602 2109-2229 Sentence denotes 'Transport through the Golgi Is Directional (One of the most compelling features of the Golgi complex ,IS its structure.
TextSentencer_T20 2230-2347 Sentence denotes In electron micrographs, the Golgi is seen #as a set of flattened cisternae with dilated rims arranged llike a stack.
T81394 2230-2347 Sentence denotes In electron micrographs, the Golgi is seen #as a set of flattened cisternae with dilated rims arranged llike a stack.
TextSentencer_T21 2348-2505 Sentence denotes The cisternae are also associated with an #array of small vesicles, as well as with a network of tubules (emanating from both sides of the stack (Figure 1 ).
T95182 2348-2505 Sentence denotes The cisternae are also associated with an #array of small vesicles, as well as with a network of tubules (emanating from both sides of the stack (Figure 1 ).
TextSentencer_T22 2506-2612 Sentence denotes Morphologically and functionally, the Golgi complex has a distinct ,polarity (Farquhar and Palade, 1981) .
T93999 2506-2612 Sentence denotes Morphologically and functionally, the Golgi complex has a distinct ,polarity (Farquhar and Palade, 1981) .
TextSentencer_T23 2613-2776 Sentence denotes Newly synthesized membrane and secretory proteins coming from the ER enter the Golgi through the cis face, traverse across the stack, and leave via the trans face.
T27232 2613-2776 Sentence denotes Newly synthesized membrane and secretory proteins coming from the ER enter the Golgi through the cis face, traverse across the stack, and leave via the trans face.
TextSentencer_T24 2777-3022 Sentence denotes A reticulum of tubules Iemanating from the trans-most cisterna, collectively referred to as the trans-Golgi network (TGN) or trans-Golgi reticulum, probably reflects the actual sites of exit (Griffiths ,and Simons, 1986; Geuze and MorrB, 1991) .
T19335 2777-3022 Sentence denotes A reticulum of tubules Iemanating from the trans-most cisterna, collectively referred to as the trans-Golgi network (TGN) or trans-Golgi reticulum, probably reflects the actual sites of exit (Griffiths ,and Simons, 1986; Geuze and MorrB, 1991) .
TextSentencer_T25 3023-3266 Sentence denotes On route ,through the Golgi, newly synthesized glycoproteins are subjected to a series of posttranslational modifications, most notably the ordered remodeling of their N-linked oli-gosaccharide side chains and biosynthesis of O-linked glycans.
T21636 3023-3266 Sentence denotes On route ,through the Golgi, newly synthesized glycoproteins are subjected to a series of posttranslational modifications, most notably the ordered remodeling of their N-linked oli-gosaccharide side chains and biosynthesis of O-linked glycans.
TextSentencer_T26 3267-3571 Sentence denotes Given the directionality of transport and the sequential nature of the glycosylation events, it is commonly thought that the Golgi consists of a series of functionally distinct compartmentscorresponding to structurally distinct cisternae or sets of cisternae (Dunphy et al., 1985; Duden et al., 1991 a) .
T18560 3267-3571 Sentence denotes Given the directionality of transport and the sequential nature of the glycosylation events, it is commonly thought that the Golgi consists of a series of functionally distinct compartmentscorresponding to structurally distinct cisternae or sets of cisternae (Dunphy et al., 1985; Duden et al., 1991 a) .
TextSentencer_T27 3572-3816 Sentence denotes Accordingly, enzymes involved in the early Golgi events in terminal N-glycosylation-such as the trimming of the high mannose chain to its mans form by mannosidase l-have been placed in the cis Golgi (Kornfeld and Kornfeld, 1985; Pelham, 1989) .
T96247 3572-3816 Sentence denotes Accordingly, enzymes involved in the early Golgi events in terminal N-glycosylation-such as the trimming of the high mannose chain to its mans form by mannosidase l-have been placed in the cis Golgi (Kornfeld and Kornfeld, 1985; Pelham, 1989) .
TextSentencer_T28 3817-4016 Sentence denotes Enzymes involved in intermediate steps, such as the transfer of N-acetylglucosamine to the mans sugars (GlcNAc transferase I), are thought to be restricted to medial cisternae (Dunphy et al., 1985) .
T38053 3817-4016 Sentence denotes Enzymes involved in intermediate steps, such as the transfer of N-acetylglucosamine to the mans sugars (GlcNAc transferase I), are thought to be restricted to medial cisternae (Dunphy et al., 1985) .
TextSentencer_T29 4017-4328 Sentence denotes Finally, enzymes that catalyze the addition of terminal galactose and sialic acid moieties (such as galactosyltransferase and sialyltransferase) are placed in trans cisternae and/or the TGN (Roth and Berger, 1982; Roth et al., 1985; Griffiths and Simons, 1986; Duncan and Kornfeld, 1988; Taatjes et al., 1988) .
T41699 4017-4328 Sentence denotes Finally, enzymes that catalyze the addition of terminal galactose and sialic acid moieties (such as galactosyltransferase and sialyltransferase) are placed in trans cisternae and/or the TGN (Roth and Berger, 1982; Roth et al., 1985; Griffiths and Simons, 1986; Duncan and Kornfeld, 1988; Taatjes et al., 1988) .
TextSentencer_T30 4329-4510 Sentence denotes The scheme thus predicts that a series of sequential biochemical reactions occurs within separate compartments, through which glycoprotein substrates pass as if on an assembly line.
T64608 4329-4510 Sentence denotes The scheme thus predicts that a series of sequential biochemical reactions occurs within separate compartments, through which glycoprotein substrates pass as if on an assembly line.
TextSentencer_T31 4511-4656 Sentence denotes A consequence of this multicompartment arrangement is that newly synthesized proteins must be transferred from one Golgi compartment to the next.
T76937 4511-4656 Sentence denotes A consequence of this multicompartment arrangement is that newly synthesized proteins must be transferred from one Golgi compartment to the next.
TextSentencer_T32 4657-4777 Sentence denotes The most widely held view is that transport vesicles bud from the dilated rims of cisternae and then fuse with the next.
T36366 4657-4777 Sentence denotes The most widely held view is that transport vesicles bud from the dilated rims of cisternae and then fuse with the next.
TextSentencer_T33 4778-4923 Sentence denotes Such a mechanism is consistent with the existence of the numerous small vesicles found in the vicinity of the Golgi (Farquhar and Palade, 1981) .
T25151 4778-4923 Sentence denotes Such a mechanism is consistent with the existence of the numerous small vesicles found in the vicinity of the Golgi (Farquhar and Palade, 1981) .
TextSentencer_T34 4924-5156 Sentence denotes Since transport of proteins and small molecules through the secretory pathway does not appear to require any identifiable signals, it is also thought that transit through the Golgi occurs by "bulk flow" (Pfeffer and Rothman, 1987) .
T12692 4924-5156 Sentence denotes Since transport of proteins and small molecules through the secretory pathway does not appear to require any identifiable signals, it is also thought that transit through the Golgi occurs by "bulk flow" (Pfeffer and Rothman, 1987) .
TextSentencer_T35 5157-5273 Sentence denotes In other words, the intercisternal transport vesicles may not selectively include components intended for transport.
T51559 5157-5273 Sentence denotes In other words, the intercisternal transport vesicles may not selectively include components intended for transport.
TextSentencer_T36 5274-5488 Sentence denotes Rather, resident proteins of any one cisterna must be selectively excluded from entering these transport vesicles, most likely reflecting the selective retention of resident proteins in their appropriate cisternae.
T61675 5274-5488 Sentence denotes Rather, resident proteins of any one cisterna must be selectively excluded from entering these transport vesicles, most likely reflecting the selective retention of resident proteins in their appropriate cisternae.
TextSentencer_T37 5489-5711 Sentence denotes A few cellular and viral glycoproteins are known that appear to have such retention signals, resulting in their accumulation in the Golgi (Colley et al., 1989; Swift and Machamer, 1991; Nilsson et al., 1991; Munro, 1991) .
T1435 5489-5711 Sentence denotes A few cellular and viral glycoproteins are known that appear to have such retention signals, resulting in their accumulation in the Golgi (Colley et al., 1989; Swift and Machamer, 1991; Nilsson et al., 1991; Munro, 1991) .
TextSentencer_T38 5712-5842 Sentence denotes Finally, at the level of the TGN, terminally glycosylated proteins are sorted to their destinations (Griffiths and Simons, 1986 ).
T81588 5712-5842 Sentence denotes Finally, at the level of the TGN, terminally glycosylated proteins are sorted to their destinations (Griffiths and Simons, 1986 ).
TextSentencer_T39 5843-5967 Sentence denotes Proteins intended for transport to lysosomes Electron micrograph is taken from Rambourg and Clermont (1990) with permission.
T88711 5843-5967 Sentence denotes Proteins intended for transport to lysosomes Electron micrograph is taken from Rambourg and Clermont (1990) with permission.
TextSentencer_T40 5968-6050 Sentence denotes The trans side is recognizable by maturing (Pg) and mature (g) secretory granules.
T96211 5968-6050 Sentence denotes The trans side is recognizable by maturing (Pg) and mature (g) secretory granules.
TextSentencer_T41 6051-6133 Sentence denotes The discontinuous profile of the fenestrated network is seen on the cis side (CE).
T96962 6051-6133 Sentence denotes The discontinuous profile of the fenestrated network is seen on the cis side (CE).
TextSentencer_T42 6134-6205 Sentence denotes Small vesicles are marked V and the endoplasmic reticulum is marked ER.
T13419 6134-6205 Sentence denotes Small vesicles are marked V and the endoplasmic reticulum is marked ER.
TextSentencer_T43 6206-6453 Sentence denotes Also notice areas where the stack is disrupted by discontinuities (48,500 x ). and endosomes are sequestered into clathrin-coated buds of the TGN, owing to specific recognition determinants (Kornfeld and Mellman, 1989; Pearse and Robinson, 1990) .
T49578 6206-6453 Sentence denotes Also notice areas where the stack is disrupted by discontinuities (48,500 x ). and endosomes are sequestered into clathrin-coated buds of the TGN, owing to specific recognition determinants (Kornfeld and Mellman, 1989; Pearse and Robinson, 1990) .
TextSentencer_T44 6454-6654 Sentence denotes Proteins lacking these signals, including soluble proteins destined for secretion, are by default packaged into transport vesicles of the constitutive pathway that are targeted to the plasma membrane.
T66346 6454-6654 Sentence denotes Proteins lacking these signals, including soluble proteins destined for secretion, are by default packaged into transport vesicles of the constitutive pathway that are targeted to the plasma membrane.
TextSentencer_T45 6655-7114 Sentence denotes In the TGN of polarized or secretory cells (endocrine and exocrine secretory cells, epithelial cells, and neurons), other routes of exit may occur, leading to inclusion either within storage granules (Kelly, 1985; Huttner and Tooze, 1989) or within transport vesicles targeted specifically to the apical or basolateral plasma membranes (Bennett et al., 1988; Wandinger-Ness et al., 1990) or to the dendritic and axonal cell surfaces (Dotti and Simons, 1990) .
T41309 6655-7114 Sentence denotes In the TGN of polarized or secretory cells (endocrine and exocrine secretory cells, epithelial cells, and neurons), other routes of exit may occur, leading to inclusion either within storage granules (Kelly, 1985; Huttner and Tooze, 1989) or within transport vesicles targeted specifically to the apical or basolateral plasma membranes (Bennett et al., 1988; Wandinger-Ness et al., 1990) or to the dendritic and axonal cell surfaces (Dotti and Simons, 1990) .
TextSentencer_T46 7115-7174 Sentence denotes How Good Is the Evidence for the Current View of the Golgi?
T43147 7115-7174 Sentence denotes How Good Is the Evidence for the Current View of the Golgi?
TextSentencer_T47 7175-7569 Sentence denotes As we have seen, there are three key elements underlying our general view of the Golgi: that the Golgi consists of several discrete compartments (cis, medial, trans, and TGN) corresponding to individual or groups of cisternae; that transit between these compartments occurs viavesicular carriers; and that the transport process is inherently nonselective with respect to the passenger proteins.
T83888 7175-7569 Sentence denotes As we have seen, there are three key elements underlying our general view of the Golgi: that the Golgi consists of several discrete compartments (cis, medial, trans, and TGN) corresponding to individual or groups of cisternae; that transit between these compartments occurs viavesicular carriers; and that the transport process is inherently nonselective with respect to the passenger proteins.
TextSentencer_T48 7570-7688 Sentence denotes Let us examine the strength of the evidence in favor of each of these propositions and interpret the data accordingly.
T64055 7570-7688 Sentence denotes Let us examine the strength of the evidence in favor of each of these propositions and interpret the data accordingly.
TextSentencer_T49 7689-7699 Sentence denotes Are There?
T79133 7689-7699 Sentence denotes Are There?
TextSentencer_T50 7700-7842 Sentence denotes Although originally thought to be a "fixation artifact," the basic cisternal organization of the Golgi complex is now accepted as a certainty.
T64165 7700-7842 Sentence denotes Although originally thought to be a "fixation artifact," the basic cisternal organization of the Golgi complex is now accepted as a certainty.
TextSentencer_T51 7843-8187 Sentence denotes Similarly, the cis to transdirectionality of transport is quite clear from early morphological and autoradiographic analysis in exocrine cells where the sidedness of the Golgi is readily identifiable (Farquhar and Palade, 1981) as well as from immunoelectron microscopy studies using viral glycoproteins as markers (Bergmann and Singer, 1983) .
T71096 7843-8187 Sentence denotes Similarly, the cis to transdirectionality of transport is quite clear from early morphological and autoradiographic analysis in exocrine cells where the sidedness of the Golgi is readily identifiable (Farquhar and Palade, 1981) as well as from immunoelectron microscopy studies using viral glycoproteins as markers (Bergmann and Singer, 1983) .
TextSentencer_T52 8188-8293 Sentence denotes What is less than clear, however, is the extent to which the Golgi is divided into distinct compartments.
T32207 8188-8293 Sentence denotes What is less than clear, however, is the extent to which the Golgi is divided into distinct compartments.
TextSentencer_T53 8294-8657 Sentence denotes As mentioned earlier, some of the enzymes involved in early, intermediate, and late steps in the terminal glycosylation of N-linked sugar chains have been localized to one to three individual cisternae by electron microscopy using immunoperoxidase or immunogold cytochemistry (Roth and Berger, 1982; Slot and Geuze, 1983; Dunphy et al., 1985; Roth et al., 1985) .
T5001 8294-8657 Sentence denotes As mentioned earlier, some of the enzymes involved in early, intermediate, and late steps in the terminal glycosylation of N-linked sugar chains have been localized to one to three individual cisternae by electron microscopy using immunoperoxidase or immunogold cytochemistry (Roth and Berger, 1982; Slot and Geuze, 1983; Dunphy et al., 1985; Roth et al., 1985) .
TextSentencer_T54 8658-8812 Sentence denotes However, a definitive demonstration that these enzymes exist in separate cisternae can only be provided by visualizing two or more enzymes simultaneously.
T45350 8658-8812 Sentence denotes However, a definitive demonstration that these enzymes exist in separate cisternae can only be provided by visualizing two or more enzymes simultaneously.
TextSentencer_T55 8813-9004 Sentence denotes The Golgi complex in the cell is not the idealized stack that we are accustomed to recognize in diagrams, but it may be subject to twists that make individual sections difficult to interpret.
T14484 8813-9004 Sentence denotes The Golgi complex in the cell is not the idealized stack that we are accustomed to recognize in diagrams, but it may be subject to twists that make individual sections difficult to interpret.
TextSentencer_T56 9005-9089 Sentence denotes To date, simultaneous localization of two or more enzymes has not been accomplished.
T85369 9005-9089 Sentence denotes To date, simultaneous localization of two or more enzymes has not been accomplished.
TextSentencer_T57 9090-9339 Sentence denotes In addition, the localization of key enzymes such as mannosidase I remains to be established; this is a critical unknown, since mannosidase I is thought to be the first glycosidase to modify N-linked oligosaccharides upon their arrival in the Golgi.
T68601 9090-9339 Sentence denotes In addition, the localization of key enzymes such as mannosidase I remains to be established; this is a critical unknown, since mannosidase I is thought to be the first glycosidase to modify N-linked oligosaccharides upon their arrival in the Golgi.
TextSentencer_T58 9340-9456 Sentence denotes A further complication is introduced by the fact that there appears to be considerable variation between cell types.
T30858 9340-9456 Sentence denotes A further complication is introduced by the fact that there appears to be considerable variation between cell types.
TextSentencer_T59 9457-9692 Sentence denotes For example, in goblet cells of the intestine, galactose a2,6-sialyltransferase (the enzyme responsible for adding l.erminal sialic acid residues to N-linked sugars) has been localized to trans cisternae, as is the case in hepatocytes.
T61723 9457-9692 Sentence denotes For example, in goblet cells of the intestine, galactose a2,6-sialyltransferase (the enzyme responsible for adding l.erminal sialic acid residues to N-linked sugars) has been localized to trans cisternae, as is the case in hepatocytes.
TextSentencer_T60 9693-9837 Sentence denotes In neighboring absorptive cells of the gut, however, almost lhe entire Golgi stack is labeled (except forthe cis cisterna) (Roth et al., 1986) .
T74626 9693-9837 Sentence denotes In neighboring absorptive cells of the gut, however, almost lhe entire Golgi stack is labeled (except forthe cis cisterna) (Roth et al., 1986) .
TextSentencer_T61 9838-9982 Sentence denotes It has also recently become clear that Golgi glycosyltransferases may have multiple isoforms with either Golgi or plasma membrane distributions.
T51840 9838-9982 Sentence denotes It has also recently become clear that Golgi glycosyltransferases may have multiple isoforms with either Golgi or plasma membrane distributions.
TextSentencer_T62 9983-10147 Sentence denotes For example, two isoforms of 81-4 galactosyltransferase have been found that differ by a 13 amino acid addition at the cytoplasmic N-terminus (Lopez et al., 1991) .
T96585 9983-10147 Sentence denotes For example, two isoforms of 81-4 galactosyltransferase have been found that differ by a 13 amino acid addition at the cytoplasmic N-terminus (Lopez et al., 1991) .
TextSentencer_T63 10148-10257 Sentence denotes The short galactosyltransferase remains in the Golgi, while the long form is directed to the plasma membrane.
T58337 10148-10257 Sentence denotes The short galactosyltransferase remains in the Golgi, while the long form is directed to the plasma membrane.
TextSentencer_T64 10258-10552 Sentence denotes Cell fractionation experiments have also contributed to our view of the Golgi as a multicompartment organelle, since it has been possible to partly separate membranes containing several of the enzymes involved in Golgi processing events (Goldberg and Kornfeld, 1983; Dunphy and Hothman, 1983) .
T56026 10258-10552 Sentence denotes Cell fractionation experiments have also contributed to our view of the Golgi as a multicompartment organelle, since it has been possible to partly separate membranes containing several of the enzymes involved in Golgi processing events (Goldberg and Kornfeld, 1983; Dunphy and Hothman, 1983) .
TextSentencer_T65 10553-10618 Sentence denotes However, interpretation of these data is limited on two accounts.
T63891 10553-10618 Sentence denotes However, interpretation of these data is limited on two accounts.
TextSentencer_T66 10619-10787 Sentence denotes First, in the absence of definitive immunocytochemical localization, it is impossible to know whether the different fractions correspond to different sets of cisternae.
T37335 10619-10787 Sentence denotes First, in the absence of definitive immunocytochemical localization, it is impossible to know whether the different fractions correspond to different sets of cisternae.
TextSentencer_T67 10788-11151 Sentence denotes Second, the enzymes studied have been separated into only three fractions, the highest density fraclions containing enzymes acting early in glycosylation (glucosidase, enzymes involved in generating mannose 6-phosphates on lysosomal enzymes) and the lightest density fractions containing terminally acting glycosyltransferases (galactosyl and sialyltransferases).
T5322 10788-11151 Sentence denotes Second, the enzymes studied have been separated into only three fractions, the highest density fraclions containing enzymes acting early in glycosylation (glucosidase, enzymes involved in generating mannose 6-phosphates on lysosomal enzymes) and the lightest density fractions containing terminally acting glycosyltransferases (galactosyl and sialyltransferases).
TextSentencer_T68 11152-11375 Sentence denotes The five enzymes 1 hat are involved in "intermediate" processing steps (manrnosidase I and II, GlcNAc transferase I, II, and IV, and fucosyltransferase) were all found to cosediment in a single peak of intermediate density.
T37121 11152-11375 Sentence denotes The five enzymes 1 hat are involved in "intermediate" processing steps (manrnosidase I and II, GlcNAc transferase I, II, and IV, and fucosyltransferase) were all found to cosediment in a single peak of intermediate density.
TextSentencer_T69 11376-11607 Sentence denotes Thus, although consistent with the existence of at least three physically and functionally distinct compartments, these observations also suggest that many of the carbohydrate processing steps may occur within a single compartment.
T52544 11376-11607 Sentence denotes Thus, although consistent with the existence of at least three physically and functionally distinct compartments, these observations also suggest that many of the carbohydrate processing steps may occur within a single compartment.
TextSentencer_T70 11608-11948 Sentence denotes Since the enzymes involved in N-glycosylation act sequentially (and specifically) (that is, mannosidase I creates the substrate for GlcNAc transferase, which creates the substrate for mannosidase II, which creates the substrate for galactosyltransferase, etc.), there is no a priori need for physical separation to ensure proper processing.
T40951 11608-11948 Sentence denotes Since the enzymes involved in N-glycosylation act sequentially (and specifically) (that is, mannosidase I creates the substrate for GlcNAc transferase, which creates the substrate for mannosidase II, which creates the substrate for galactosyltransferase, etc.), there is no a priori need for physical separation to ensure proper processing.
TextSentencer_T71 11949-12179 Sentence denotes Indeed, having GlcNAc transferase and galactosyltransferase in a common compartment would explain the existence of lactosamine repeats in the terminal chains of many glycoproteins (Cummings and Kornfeld, 1984; Howe et al., 1988) .
T60775 11949-12179 Sentence denotes Indeed, having GlcNAc transferase and galactosyltransferase in a common compartment would explain the existence of lactosamine repeats in the terminal chains of many glycoproteins (Cummings and Kornfeld, 1984; Howe et al., 1988) .
TextSentencer_T72 12180-12463 Sentence denotes A further reason for caution in interpreting existing imlmunocytochemistry and fractionation results is the growing appreciation of the fact that the individual Golgi cister-Inae-and perhaps even entire stacks-may not be as datic and structurally distinct as we have come to believe.
T25926 12180-12463 Sentence denotes A further reason for caution in interpreting existing imlmunocytochemistry and fractionation results is the growing appreciation of the fact that the individual Golgi cister-Inae-and perhaps even entire stacks-may not be as datic and structurally distinct as we have come to believe.
TextSentencer_T73 12464-12660 Sentence denotes IExamination of the Golgi using high voltage electron milcroscopy has suggested that adjacent stacks of cisternae (are joined via extensive tubular interconnections (Rambourg and Clermont, 1990) .
T95562 12464-12660 Sentence denotes IExamination of the Golgi using high voltage electron milcroscopy has suggested that adjacent stacks of cisternae (are joined via extensive tubular interconnections (Rambourg and Clermont, 1990) .
TextSentencer_T74 12661-12932 Sentence denotes Similarly, real-time imaging of Iliving cells labeled with the fluorescent lipid analog NBD-Iceramide has revealed that the Golgi is capable of forming ,a large number of tubules that may serve to connect other-'wise "separate" stacks of cisternae (Cooper et al., 1990) .
T41740 12661-12932 Sentence denotes Similarly, real-time imaging of Iliving cells labeled with the fluorescent lipid analog NBD-Iceramide has revealed that the Golgi is capable of forming ,a large number of tubules that may serve to connect other-'wise "separate" stacks of cisternae (Cooper et al., 1990) .
TextSentencer_T75 12933-13083 Sentence denotes Whether the tubules form connections between cisternae in register (i.e., cis to cis, medial to medial) or out of register (cis to medial) is unknown.
T34409 12933-13083 Sentence denotes Whether the tubules form connections between cisternae in register (i.e., cis to cis, medial to medial) or out of register (cis to medial) is unknown.
TextSentencer_T76 13084-13244 Sentence denotes The possibility must also be considered that even within a single stack, adjacent cisternae might at least transiently possess similar tubular interconnections.
T30429 13084-13244 Sentence denotes The possibility must also be considered that even within a single stack, adjacent cisternae might at least transiently possess similar tubular interconnections.
TextSentencer_T77 13245-13252 Sentence denotes Anyway?
T77350 13245-13252 Sentence denotes Anyway?
TextSentencer_T78 13253-13355 Sentence denotes A question that clearly needs discussion at this point is what exactly defines a cellular compartment.
T68179 13253-13355 Sentence denotes A question that clearly needs discussion at this point is what exactly defines a cellular compartment.
TextSentencer_T79 13356-13541 Sentence denotes Classically, membrane-bounded compartments have been viewed as comprising physically distinct entities each with its own distinct protein compositions and, presumably, unique functions.
T3251 13356-13541 Sentence denotes Classically, membrane-bounded compartments have been viewed as comprising physically distinct entities each with its own distinct protein compositions and, presumably, unique functions.
TextSentencer_T80 13542-13692 Sentence denotes Accordingly, all of any one type of organelle can be considered a compartment, but so can a distinct region (or "subcompartment") within an organelle.
T63075 13542-13692 Sentence denotes Accordingly, all of any one type of organelle can be considered a compartment, but so can a distinct region (or "subcompartment") within an organelle.
TextSentencer_T81 13693-13834 Sentence denotes By this criterion, compartment boundaries should be easily delineated by immunoelectron microscopic localization of resident marker proteins.
T25519 13693-13834 Sentence denotes By this criterion, compartment boundaries should be easily delineated by immunoelectron microscopic localization of resident marker proteins.
TextSentencer_T82 13835-13895 Sentence denotes However, this simple view is complicated by several factors.
T27093 13835-13895 Sentence denotes However, this simple view is complicated by several factors.
TextSentencer_T83 13896-14111 Sentence denotes For example, even the localization of two Golgi enzymes to different cisternae by double label immunoelectron microscopy might not unequivocally demonstrate that they are present in physically distinct compartments.
T46309 13896-14111 Sentence denotes For example, even the localization of two Golgi enzymes to different cisternae by double label immunoelectron microscopy might not unequivocally demonstrate that they are present in physically distinct compartments.
TextSentencer_T84 14112-14309 Sentence denotes Such a distribution of enzymes could reflect the existence of subdomains in an otherwise continuous membrane array, analogous to the lateral heterogeneity found between the rough and the smooth ER.
T12946 14112-14309 Sentence denotes Such a distribution of enzymes could reflect the existence of subdomains in an otherwise continuous membrane array, analogous to the lateral heterogeneity found between the rough and the smooth ER.
TextSentencer_T85 14310-14512 Sentence denotes Conversely, markers may be segregated into physically distinct membranes that nevertheless remain functionally continuous by repeated membrane fissions and fusions or transient tubular interconnections.
T94802 14310-14512 Sentence denotes Conversely, markers may be segregated into physically distinct membranes that nevertheless remain functionally continuous by repeated membrane fissions and fusions or transient tubular interconnections.
TextSentencer_T86 14513-14700 Sentence denotes The existence of such homotypic interactions-interactions among "like" elements-would play an important role in preserving continuity among equivalent but physically separated organelles.
T7374 14513-14700 Sentence denotes The existence of such homotypic interactions-interactions among "like" elements-would play an important role in preserving continuity among equivalent but physically separated organelles.
TextSentencer_T87 14701-14834 Sentence denotes Thus, the simple test of localizing different markers to distinct membranes cannot by itself serve to identify distinct compartments.
T93447 14701-14834 Sentence denotes Thus, the simple test of localizing different markers to distinct membranes cannot by itself serve to identify distinct compartments.
TextSentencer_T88 14835-14960 Sentence denotes The definition of a compartment is further confounded when considering organelles that are also involved in membrane traffic.
T59614 14835-14960 Sentence denotes The definition of a compartment is further confounded when considering organelles that are also involved in membrane traffic.
TextSentencer_T89 14961-15181 Sentence denotes Given that there is likely to be continuous transport and recycling of membrane components between such compartments, compartment identities are not static and therefore may not always be entirely biochemically distinct.
T38145 14961-15181 Sentence denotes Given that there is likely to be continuous transport and recycling of membrane components between such compartments, compartment identities are not static and therefore may not always be entirely biochemically distinct.
TextSentencer_T90 15182-15290 Sentence denotes The object, then, is to identify only those components that are endogenous, i.e., not involved in recycling.
T91144 15182-15290 Sentence denotes The object, then, is to identify only those components that are endogenous, i.e., not involved in recycling.
TextSentencer_T91 15291-15480 Sentence denotes Conceivably, endogenous (or resident) components may be defined by their ability to interact with a compartment-specific structural framework, such as a cytosolic membrane coat or skeleton.
T27554 15291-15480 Sentence denotes Conceivably, endogenous (or resident) components may be defined by their ability to interact with a compartment-specific structural framework, such as a cytosolic membrane coat or skeleton.
TextSentencer_T92 15481-15684 Sentence denotes It is clear that only by identifying the machinery responsible for entry into, retention within, or exit from a compartment will we be able to precisely and consistently determine compartment boundaries.
T86209 15481-15684 Sentence denotes It is clear that only by identifying the machinery responsible for entry into, retention within, or exit from a compartment will we be able to precisely and consistently determine compartment boundaries.
TextSentencer_T93 15685-15950 Sentence denotes In the absence of this information, compartments can only be tentatively defined as functionally equivalent and possibly physically continuous populations of membrane-bounded structures that are both functionally and physically distinct from all other compartments.
T80527 15685-15950 Sentence denotes In the absence of this information, compartments can only be tentatively defined as functionally equivalent and possibly physically continuous populations of membrane-bounded structures that are both functionally and physically distinct from all other compartments.
TextSentencer_T94 15951-16009 Sentence denotes Taken from Rambourg and Clermont (1990) , with permission.
T63372 15951-16009 Sentence denotes Taken from Rambourg and Clermont (1990) , with permission.
TextSentencer_T95 16010-16175 Sentence denotes The osmiophilic cis compartment, the saccules (cisternae) of the medial compartment, as well as the cisternae and tubules of the trans compartment are all indicated.
T34007 16010-16175 Sentence denotes The osmiophilic cis compartment, the saccules (cisternae) of the medial compartment, as well as the cisternae and tubules of the trans compartment are all indicated.
TextSentencer_T96 16176-16405 Sentence denotes scribe definitively the compartmentalization of the Golgi complex, models for the organization of the Golgi should be kept as simple as possible, adding complexity only as it is necessitated by additional functional requirements.
T2643 16176-16405 Sentence denotes scribe definitively the compartmentalization of the Golgi complex, models for the organization of the Golgi should be kept as simple as possible, adding complexity only as it is necessitated by additional functional requirements.
TextSentencer_T97 16406-16762 Sentence denotes As we have discussed, there are three minimal functions that the Golgi must accomplish: first, receipt and sorting of membrane and soluble cargo arriving at the cis Golgi from the ER; second, glycosylation and processing of glycoproteins and glycolipids; and third, sorting of membrane and soluble cargo arriving and exiting at the trans face of the Golgi.
T41331 16406-16762 Sentence denotes As we have discussed, there are three minimal functions that the Golgi must accomplish: first, receipt and sorting of membrane and soluble cargo arriving at the cis Golgi from the ER; second, glycosylation and processing of glycoproteins and glycolipids; and third, sorting of membrane and soluble cargo arriving and exiting at the trans face of the Golgi.
TextSentencer_T98 16763-16974 Sentence denotes Assuming that distinct compartments are required to accomplish these functions, at least three compartments are required, defined here as the cis-Golgi network (CGN), the medial Golgi, and the TGN, respectively.
T1177 16763-16974 Sentence denotes Assuming that distinct compartments are required to accomplish these functions, at least three compartments are required, defined here as the cis-Golgi network (CGN), the medial Golgi, and the TGN, respectively.
TextSentencer_T99 16975-17276 Sentence denotes Although the details of Golgi morphology vary considerably between different cell types, such a three compartment subdivision is generally consistent with the overall structural organization of the mammalian Golgi from threedimensional reconstructions (Rambourg and Clermont, 1990) (Figures 2 and 3) .
T94299 16975-17276 Sentence denotes Although the details of Golgi morphology vary considerably between different cell types, such a three compartment subdivision is generally consistent with the overall structural organization of the mammalian Golgi from threedimensional reconstructions (Rambourg and Clermont, 1990) (Figures 2 and 3) .
TextSentencer_T100 17277-17525 Sentence denotes It is also consistent with the functional organization of the Golgi in Saccharomyces cerevisiae, which, on the basis of mutations affecting Golgi function, has recently been proposed toconsist of at least three compartments (Graham and Emr, 1991) .
T83890 17277-17525 Sentence denotes It is also consistent with the functional organization of the Golgi in Saccharomyces cerevisiae, which, on the basis of mutations affecting Golgi function, has recently been proposed toconsist of at least three compartments (Graham and Emr, 1991) .
TextSentencer_T101 17526-17651 Sentence denotes The CGN At a minimum, the cis side of the Golgi stack must function in the receipt of newly synthesized material from the ER.
T17347 17526-17651 Sentence denotes The CGN At a minimum, the cis side of the Golgi stack must function in the receipt of newly synthesized material from the ER.
TextSentencer_T102 17652-17896 Sentence denotes Structurally, however, the cis-most cisterna of the Golgi is typically associated with a continuous array of tubules that are selectively stained after prolonged osmication (Lindsey and Ellisman, 1985; Rambourg and Clermont, 1990) ( Figure 2 ).
T34119 17652-17896 Sentence denotes Structurally, however, the cis-most cisterna of the Golgi is typically associated with a continuous array of tubules that are selectively stained after prolonged osmication (Lindsey and Ellisman, 1985; Rambourg and Clermont, 1990) ( Figure 2 ).
TextSentencer_T103 17897-18104 Sentence denotes Given this distinctive morphology, and by analogy to the TGN, it seems appropriate to refer to this region as a distinct compartment called the CGN (Huttner and Tooze, 1989; Hsu et al., 1991; Pelham, 1991) .
T65484 17897-18104 Sentence denotes Given this distinctive morphology, and by analogy to the TGN, it seems appropriate to refer to this region as a distinct compartment called the CGN (Huttner and Tooze, 1989; Hsu et al., 1991; Pelham, 1991) .
TextSentencer_T104 18105-18369 Sentence denotes For several reasons, it also seems reasonable to suggest that the CGN also includes the poorly understood but possibly interconnected system of tubules between the ER and the Golgi, referred to as the "salvage compartment" (Warren, 1987; Pelham, 1991) (Figure 3 ).
T6056 18105-18369 Sentence denotes For several reasons, it also seems reasonable to suggest that the CGN also includes the poorly understood but possibly interconnected system of tubules between the ER and the Golgi, referred to as the "salvage compartment" (Warren, 1987; Pelham, 1991) (Figure 3 ).
TextSentencer_T105 18370-18597 Sentence denotes In addition to serving as a site of entry into the Golgi, recent evidence suggests that the CGN functions in the recycling of protein and lipid components back to the ER, while having a relatively limited role in glycosylation.
T92425 18370-18597 Sentence denotes In addition to serving as a site of entry into the Golgi, recent evidence suggests that the CGN functions in the recycling of protein and lipid components back to the ER, while having a relatively limited role in glycosylation.
TextSentencer_T106 18598-18833 Sentence denotes Using both animal and yeast cells, Pelham and colleagues have found that soluble ER proteins containing the KDEL (or HDEL) ER retention marker are delivered to a post-ER The ports of exit are the sites from which proteins leave the ER.
T65946 18598-18833 Sentence denotes Using both animal and yeast cells, Pelham and colleagues have found that soluble ER proteins containing the KDEL (or HDEL) ER retention marker are delivered to a post-ER The ports of exit are the sites from which proteins leave the ER.
TextSentencer_T107 18834-19085 Sentence denotes As discussed in the text, the "intermediate compartment" defined by the p53 and ~58 antigens probably consists both of the CGN, the ports of exit from the ER, and the carrier elements responsible for bidirectional transport between the ER and the CGN.
T42791 18834-19085 Sentence denotes As discussed in the text, the "intermediate compartment" defined by the p53 and ~58 antigens probably consists both of the CGN, the ports of exit from the ER, and the carrier elements responsible for bidirectional transport between the ER and the CGN.
TextSentencer_T108 19086-19231 Sentence denotes The lateral arrows would be sites where direct fusions would interconnect CGN-CGN, medialmedial, and TGN-TGN compartments of two adjacent stacks.
T57918 19086-19231 Sentence denotes The lateral arrows would be sites where direct fusions would interconnect CGN-CGN, medialmedial, and TGN-TGN compartments of two adjacent stacks.
TextSentencer_T109 19232-19466 Sentence denotes Compare these sites to the discontinuities in Figure 1 . site, in which little "Golgi-like" oligosaccharide processing oiccurs and from which these proteins are returned to the ER (Pelham, 1988 (Pelham, , 1989 Dean and Pelham, 1990) .
T62390 19232-19466 Sentence denotes Compare these sites to the discontinuities in Figure 1 . site, in which little "Golgi-like" oligosaccharide processing oiccurs and from which these proteins are returned to the ER (Pelham, 1988 (Pelham, , 1989 Dean and Pelham, 1990) .
TextSentencer_T110 19467-19650 Sentence denotes In animal cells, the lysosomal enzyme cathepsin D was given a C-terminal KDEL tag and found not to receive any terminal sugar modifications associated with Golgi-linked glycosylation.
T79754 19467-19650 Sentence denotes In animal cells, the lysosomal enzyme cathepsin D was given a C-terminal KDEL tag and found not to receive any terminal sugar modifications associated with Golgi-linked glycosylation.
TextSentencer_T111 19651-19722 Sentence denotes However, mannose residues on the enzyme did receive a GlcNAc-phosphate.
T12580 19651-19722 Sentence denotes However, mannose residues on the enzyme did receive a GlcNAc-phosphate.
TextSentencer_T112 19723-19919 Sentence denotes Thus, although the KDEL clonstruct reached a GlcNAc-phosphotransferase-containing compartment, it did not encounter mannosidase I, a glycosidase that would remove the phosphotransferase substrate.
T93549 19723-19919 Sentence denotes Thus, although the KDEL clonstruct reached a GlcNAc-phosphotransferase-containing compartment, it did not encounter mannosidase I, a glycosidase that would remove the phosphotransferase substrate.
TextSentencer_T113 19920-20211 Sentence denotes Although it may yet turn out that some KDEL proteins receive further oligosaccharide modifications, K.DEL receptors can retrieve these proteins before they reach the bulk of the oligosaccharide transferases; thus, recycling is a function associated with a distinct "early" Golgi compartment.
T46932 19920-20211 Sentence denotes Although it may yet turn out that some KDEL proteins receive further oligosaccharide modifications, K.DEL receptors can retrieve these proteins before they reach the bulk of the oligosaccharide transferases; thus, recycling is a function associated with a distinct "early" Golgi compartment.
TextSentencer_T114 20212-20385 Sentence denotes Without immunocytochemical localization of these constructs (the KDEL receptor or the phosphotransferase), it is impossible to be certain that these events occur in the CGN.
T71017 20212-20385 Sentence denotes Without immunocytochemical localization of these constructs (the KDEL receptor or the phosphotransferase), it is impossible to be certain that these events occur in the CGN.
TextSentencer_T115 20386-20695 Sentence denotes However, this appears likely, given that our model assumes that the tubules and vesicles defining the CGN are also associated with antigens such as ~53, ~58, and mb2 (Saraste et al., 1987; Schweizer et al., 1988; Chavrier et al., 1990) which have been used to define the so-called "intermediate compartment" .
T32730 20386-20695 Sentence denotes However, this appears likely, given that our model assumes that the tubules and vesicles defining the CGN are also associated with antigens such as ~53, ~58, and mb2 (Saraste et al., 1987; Schweizer et al., 1988; Chavrier et al., 1990) which have been used to define the so-called "intermediate compartment" .
TextSentencer_T116 20696-20906 Sentence denotes These antigens label structures that appear to serve as intermediates in transport from the ER to the Golgi as well a.s in the recycling of Golgi components back to the ER (I-ippincott- Schwartz et al., 1990) .
T59883 20696-20906 Sentence denotes These antigens label structures that appear to serve as intermediates in transport from the ER to the Golgi as well a.s in the recycling of Golgi components back to the ER (I-ippincott- Schwartz et al., 1990) .
TextSentencer_T117 20907-21186 Sentence denotes The markers also label presumed sites of exit from the ER ("transitional elements," Palade, 1975) as well as the cis-most Golgi cisterna (Saraste and Svensson, 1991; Lotti et al., 1992) , suggesting that they are not endogenous CGN components, but recycle between the ER and CGN.
T92375 20907-21186 Sentence denotes The markers also label presumed sites of exit from the ER ("transitional elements," Palade, 1975) as well as the cis-most Golgi cisterna (Saraste and Svensson, 1991; Lotti et al., 1992) , suggesting that they are not endogenous CGN components, but recycle between the ER and CGN.
TextSentencer_T118 21187-21415 Sentence denotes Thus, the intermediate compartment probably comprises the exit sites from both the E.R and the CGN as well as the dynamic "pool" of vesicles and tubules that reflects the continuous recycling between tlhe two sites ( Figure 3) .
T94192 21187-21415 Sentence denotes Thus, the intermediate compartment probably comprises the exit sites from both the E.R and the CGN as well as the dynamic "pool" of vesicles and tubules that reflects the continuous recycling between tlhe two sites ( Figure 3) .
TextSentencer_T119 21416-21662 Sentence denotes Although incubation at low temperalture has also been used to delineate boundaries in this region, like all temperature blocks, forward transport is clependent on length of incubation, making precise interpretation even more difficult than usual.
T35309 21416-21662 Sentence denotes Although incubation at low temperalture has also been used to delineate boundaries in this region, like all temperature blocks, forward transport is clependent on length of incubation, making precise interpretation even more difficult than usual.
TextSentencer_T120 21663-21784 Sentence denotes We thus view the CGN as a unique Golgi compartment responsible for receiving and sorting components arriving from the ER.
T31676 21663-21784 Sentence denotes We thus view the CGN as a unique Golgi compartment responsible for receiving and sorting components arriving from the ER.
TextSentencer_T121 21785-22003 Sentence denotes Structurally, we predict it will ordinarily (but perhaps not always) consist of the cis-most Golgi cisterna and the associated vesicles and tubules that include the intermediate compartment of Schweizer et al. (1990) .
T23365 21785-22003 Sentence denotes Structurally, we predict it will ordinarily (but perhaps not always) consist of the cis-most Golgi cisterna and the associated vesicles and tubules that include the intermediate compartment of Schweizer et al. (1990) .
TextSentencer_T122 22004-22309 Sentence denotes In addition to the transport of KDEL-tagged proteins to and from the Golgi and the limited post-ER glycosylation events to which these proteins are subjected, the CGN rnight also be predicted to include a variety of other activities that have been relegated to the purgatory between the EIR and the Golgi.
T30303 22004-22309 Sentence denotes In addition to the transport of KDEL-tagged proteins to and from the Golgi and the limited post-ER glycosylation events to which these proteins are subjected, the CGN rnight also be predicted to include a variety of other activities that have been relegated to the purgatory between the EIR and the Golgi.
TextSentencer_T123 22310-22601 Sentence denotes These would include the addition of the first N-acetylgalactosamine residue to O-linked sugars, the assembly of coronavirus particles (Tooze et al., 1988; Machamer et al., 1990) and fatty acylation of membrane protein cytoplasmic domains (Rizzolo and Kornfeld, 1988; E3onatti et al., 1989) .
T31114 22310-22601 Sentence denotes These would include the addition of the first N-acetylgalactosamine residue to O-linked sugars, the assembly of coronavirus particles (Tooze et al., 1988; Machamer et al., 1990) and fatty acylation of membrane protein cytoplasmic domains (Rizzolo and Kornfeld, 1988; E3onatti et al., 1989) .
TextSentencer_T124 22602-22749 Sentence denotes Experiments in yeast also give at least indirect support to the existence of lipid recycling to the ER from the CGN as well (Cleves et al., 1991) .
T68673 22602-22749 Sentence denotes Experiments in yeast also give at least indirect support to the existence of lipid recycling to the ER from the CGN as well (Cleves et al., 1991) .
TextSentencer_T125 22750-22818 Sentence denotes The medial Golgi would function primarily as a glycosylation device.
T87435 22750-22818 Sentence denotes The medial Golgi would function primarily as a glycosylation device.
TextSentencer_T126 22819-23001 Sentence denotes Structurally, it corresponds to the cisternae and tubules in the middle of the Golgi stack (Figure 3 ) whose structures vary widely in different cells (Rambourg and Clermont, 1990) .
T81932 22819-23001 Sentence denotes Structurally, it corresponds to the cisternae and tubules in the middle of the Golgi stack (Figure 3 ) whose structures vary widely in different cells (Rambourg and Clermont, 1990) .
TextSentencer_T127 23002-23231 Sentence denotes While distinct from the CGN or TGN, we assume that the medial cisternae represent a single functionally continuous compartment, irrespective of the actual number of physically separate cisternal elements in any one Golgi complex.
T93460 23002-23231 Sentence denotes While distinct from the CGN or TGN, we assume that the medial cisternae represent a single functionally continuous compartment, irrespective of the actual number of physically separate cisternal elements in any one Golgi complex.
TextSentencer_T128 23232-23337 Sentence denotes Nevertheless, owing to the sidedness of the Golgi, the medial cisternae may appear structurally distinct.
T5607 23232-23337 Sentence denotes Nevertheless, owing to the sidedness of the Golgi, the medial cisternae may appear structurally distinct.
TextSentencer_T129 23338-23566 Sentence denotes For example, since one face of a medial cisterna is apposed to the CGN while another face is apposed to the TGN, the two faces may have different compositions, owing to their interactions with structurally distinct compartments.
T72027 23338-23566 Sentence denotes For example, since one face of a medial cisterna is apposed to the CGN while another face is apposed to the TGN, the two faces may have different compositions, owing to their interactions with structurally distinct compartments.
TextSentencer_T130 23567-23779 Sentence denotes Most of the glycosylation reactions (N-linked, O-linked, as well as glycolipid synthesis), aswell as polysaccharide synthesis normally associated with the Golgi, are viewed as occurring in the medial compartment.
T85806 23567-23779 Sentence denotes Most of the glycosylation reactions (N-linked, O-linked, as well as glycolipid synthesis), aswell as polysaccharide synthesis normally associated with the Golgi, are viewed as occurring in the medial compartment.
TextSentencer_T131 23780-23926 Sentence denotes This arrangement would account for cell type heterogeneity in cisternal number and enzyme distribution by placing them all in asingle compartment.
T19751 23780-23926 Sentence denotes This arrangement would account for cell type heterogeneity in cisternal number and enzyme distribution by placing them all in asingle compartment.
TextSentencer_T132 23927-24001 Sentence denotes At present, there is insufficient data to know if this is really the case.
T96044 23927-24001 Sentence denotes At present, there is insufficient data to know if this is really the case.
TextSentencer_T133 24002-24114 Sentence denotes If the medial Golgi serves only to mediate glycosylation reactions, why the characteristic cisternal morphology?
T80451 24002-24114 Sentence denotes If the medial Golgi serves only to mediate glycosylation reactions, why the characteristic cisternal morphology?
TextSentencer_T134 24115-24190 Sentence denotes One possibility might be simply to enhance the efficiency of glycosylation.
T76790 24115-24190 Sentence denotes One possibility might be simply to enhance the efficiency of glycosylation.
TextSentencer_T135 24191-24348 Sentence denotes Although precise measurements are difficult to make, transport systems for sugar nucleotide precursors are kinetically inefficient (Deutscher et al., 1984) .
T560 24191-24348 Sentence denotes Although precise measurements are difficult to make, transport systems for sugar nucleotide precursors are kinetically inefficient (Deutscher et al., 1984) .
TextSentencer_T136 24349-24565 Sentence denotes Moreover, while the terminal transferases also have relatively high K,s for substrate (high micromolar range), they may work at rates that may exceed the rate of sugar nucleotide transport (Weinstein et al., 1982; C.
T92542 24349-24565 Sentence denotes Moreover, while the terminal transferases also have relatively high K,s for substrate (high micromolar range), they may work at rates that may exceed the rate of sugar nucleotide transport (Weinstein et al., 1982; C.
TextSentencer_T137 24566-24603 Sentence denotes Hirschberg, personal communication) .
T95526 24566-24603 Sentence denotes Hirschberg, personal communication) .
TextSentencer_T138 24604-24776 Sentence denotes Thus, the cisternal stack by its flattened structure may serve to enhance the efficiency of glycosylation by minimizing lumenal volume and increasing membrane surface area.
T38586 24604-24776 Sentence denotes Thus, the cisternal stack by its flattened structure may serve to enhance the efficiency of glycosylation by minimizing lumenal volume and increasing membrane surface area.
TextSentencer_T139 24777-24882 Sentence denotes The TGN is viewed as the compartment that mediates the sorting and final exit of material from the Golgi.
T62697 24777-24882 Sentence denotes The TGN is viewed as the compartment that mediates the sorting and final exit of material from the Golgi.
TextSentencer_T140 24883-25091 Sentence denotes Structurally, it is likely to be defined by the sacculotubular network located on the trans side of the Golgi that varies in structure in different cell types (Rambourg and Clermont, 1990) (Figures 2 and 3) .
T27564 24883-25091 Sentence denotes Structurally, it is likely to be defined by the sacculotubular network located on the trans side of the Golgi that varies in structure in different cell types (Rambourg and Clermont, 1990) (Figures 2 and 3) .
TextSentencer_T141 25092-25350 Sentence denotes The TGN can be visualized in the electron microscope after labeling cells with Cs-NBD-ceramide (Pagan0 et al., 1989) with Cs-DMB-ceramide (Pagan0 et al., 1991) or after accumulating vesicular stomatitis virus (VSV) G protein at 20% (Griffiths et al., 1985) .
T88787 25092-25350 Sentence denotes The TGN can be visualized in the electron microscope after labeling cells with Cs-NBD-ceramide (Pagan0 et al., 1989) with Cs-DMB-ceramide (Pagan0 et al., 1991) or after accumulating vesicular stomatitis virus (VSV) G protein at 20% (Griffiths et al., 1985) .
TextSentencer_T142 25351-25456 Sentence denotes The TGN may also have a lower pH than preceding compartments in the pathway (Anderson and Pathak, 1985) .
T58298 25351-25456 Sentence denotes The TGN may also have a lower pH than preceding compartments in the pathway (Anderson and Pathak, 1985) .
TextSentencer_T143 25457-25603 Sentence denotes The TGN is known to undergo dynamic changes in size, depending on the amount of protein traffic through the compartment (Griffiths et al., 1989) .
T793 25457-25603 Sentence denotes The TGN is known to undergo dynamic changes in size, depending on the amount of protein traffic through the compartment (Griffiths et al., 1989) .
TextSentencer_T144 25604-25801 Sentence denotes In glandular cells producing secretion granules, several cisternae on the trans side form condensing vacuoles, presuming that all these cisternae are part of the TGN (Rambourg and Clermont, 1990) .
T85162 25604-25801 Sentence denotes In glandular cells producing secretion granules, several cisternae on the trans side form condensing vacuoles, presuming that all these cisternae are part of the TGN (Rambourg and Clermont, 1990) .
TextSentencer_T145 25802-25953 Sentence denotes The extreme case is represented by the Golgi complex of algae where flakes are assembled in the lumen of the Golgi cisternae (Melkonian et al., 1991) .
T48653 25802-25953 Sentence denotes The extreme case is represented by the Golgi complex of algae where flakes are assembled in the lumen of the Golgi cisternae (Melkonian et al., 1991) .
TextSentencer_T146 25954-26206 Sentence denotes Since these large flakes are first observed several cisternae away from the cis side, it seems reasonable to assume that the flakes assemble in saccular portions of the TGN and that entire TGN cisternae peel off and are transported to the cell surface.
T20038 25954-26206 Sentence denotes Since these large flakes are first observed several cisternae away from the cis side, it seems reasonable to assume that the flakes assemble in saccular portions of the TGN and that entire TGN cisternae peel off and are transported to the cell surface.
TextSentencer_T147 26207-26370 Sentence denotes The main function of the TGN is to sort proteins and lipids leaving for different post-Golgi destinations (Griffiths and Simons, 1986; Simons and van Meer, 1988) .
T4614 26207-26370 Sentence denotes The main function of the TGN is to sort proteins and lipids leaving for different post-Golgi destinations (Griffiths and Simons, 1986; Simons and van Meer, 1988) .
TextSentencer_T148 26371-26659 Sentence denotes The TGN also receives membrane traffic from the endocytic pathway (Farquhar and Palade, 1981; Kornfeld and Mellman, 1989 ) and, unlike all other Golgi subcompartments, its degree of continuity with the plasma membrane is increased following treatment with brefeldin A (BFA) (Lippincott- .
T89864 26371-26659 Sentence denotes The TGN also receives membrane traffic from the endocytic pathway (Farquhar and Palade, 1981; Kornfeld and Mellman, 1989 ) and, unlike all other Golgi subcompartments, its degree of continuity with the plasma membrane is increased following treatment with brefeldin A (BFA) (Lippincott- .
TextSentencer_T149 26660-26821 Sentence denotes The TGN is also the only Golgi compartment that fails to enter the ER following BFA (Chege and Pfeffer, 1990; Ulmer and Palade, 1991; Reaves and Banting, 1992) .
T44313 26660-26821 Sentence denotes The TGN is also the only Golgi compartment that fails to enter the ER following BFA (Chege and Pfeffer, 1990; Ulmer and Palade, 1991; Reaves and Banting, 1992) .
TextSentencer_T150 26822-27123 Sentence denotes Certain "late" protein modification events also occur in the TGN, such as galactose a2,6 sialylation (Duncan and Kornfeld, 1988 ) tyrosine sulfation (Huttner and Baeuerle, 1988) and proteolytic cleavage at dibasic residues on viral glycoproteins and cellular precursor proteins (Sossin et al., 1990) .
T24710 26822-27123 Sentence denotes Certain "late" protein modification events also occur in the TGN, such as galactose a2,6 sialylation (Duncan and Kornfeld, 1988 ) tyrosine sulfation (Huttner and Baeuerle, 1988) and proteolytic cleavage at dibasic residues on viral glycoproteins and cellular precursor proteins (Sossin et al., 1990) .
TextSentencer_T151 27124-27275 Sentence denotes We propose that the TGN also operates as a directional valve to control the flow of membrane proteins and lipids in biosynthetic transport (Figure 3) .
T83333 27124-27275 Sentence denotes We propose that the TGN also operates as a directional valve to control the flow of membrane proteins and lipids in biosynthetic transport (Figure 3) .
TextSentencer_T152 27276-27450 Sentence denotes Such a function would contribute to the efficiency of forward transport by preventing passenger proteins and lipids from returning to the medial Golgi after reaching the TGN.
T82476 27276-27450 Sentence denotes Such a function would contribute to the efficiency of forward transport by preventing passenger proteins and lipids from returning to the medial Golgi after reaching the TGN.
TextSentencer_T153 27451-27543 Sentence denotes In practice, this would predict that there is no recycling from the TGN to the medial Golgi.
T85164 27451-27543 Sentence denotes In practice, this would predict that there is no recycling from the TGN to the medial Golgi.
TextSentencer_T154 27544-27674 Sentence denotes The need for this function is best illustrated by considering the transport and distribution of membrane lipids through the Golgi.
T82120 27544-27674 Sentence denotes The need for this function is best illustrated by considering the transport and distribution of membrane lipids through the Golgi.
TextSentencer_T155 27675-27850 Sentence denotes Several lipids such as cholesterol, glycolipids, and sphingomyelin are present in very low concentrations in the ER, although they are abundant in the Golgi (van Meer, 1989) .
T79891 27675-27850 Sentence denotes Several lipids such as cholesterol, glycolipids, and sphingomyelin are present in very low concentrations in the ER, although they are abundant in the Golgi (van Meer, 1989) .
TextSentencer_T156 27851-27986 Sentence denotes If there were lipid recycling from each Golgi compartment, it would be difficult to account for these differences in lipid composition.
T55416 27851-27986 Sentence denotes If there were lipid recycling from each Golgi compartment, it would be difficult to account for these differences in lipid composition.
TextSentencer_T157 27987-28066 Sentence denotes Placing a valve in the pathway makes the lipid sorting problem easier to solve.
T36285 27987-28066 Sentence denotes Placing a valve in the pathway makes the lipid sorting problem easier to solve.
TextSentencer_T158 28067-28279 Sentence denotes Several studies have demonstrated directly that there is little backflow of glycoproteins from the TGN into proximal Golgi compartments (Duncan and Kornfeld, 1988; Neefjes et al., 1988; Chege and Pfeffer, 1990) .
T59211 28067-28279 Sentence denotes Several studies have demonstrated directly that there is little backflow of glycoproteins from the TGN into proximal Golgi compartments (Duncan and Kornfeld, 1988; Neefjes et al., 1988; Chege and Pfeffer, 1990) .
TextSentencer_T159 28280-28552 Sentence denotes Also, recycling of glycosphingolipids through the TGN (Schwartzmann and Sandhoff, 1990) would be easier to explain if these plasma membrane lipids would not encouter medial Golgi enzymes; otherwise, with time, only complex glycolipids would be present on the cell surface.
T85020 28280-28552 Sentence denotes Also, recycling of glycosphingolipids through the TGN (Schwartzmann and Sandhoff, 1990) would be easier to explain if these plasma membrane lipids would not encouter medial Golgi enzymes; otherwise, with time, only complex glycolipids would be present on the cell surface.
TextSentencer_T160 28553-28613 Sentence denotes Does Transport through the Golgi Require Vesicular Carriers?
T40574 28553-28613 Sentence denotes Does Transport through the Golgi Require Vesicular Carriers?
TextSentencer_T161 28614-28765 Sentence denotes The second key element underlying our current view of the Golgi concerns the role of carrier vesicles in mediating transport through the Golgi complex.
T72171 28614-28765 Sentence denotes The second key element underlying our current view of the Golgi concerns the role of carrier vesicles in mediating transport through the Golgi complex.
TextSentencer_T162 28766-28972 Sentence denotes While transport vesicles may represent the most likely mechanism to accomplish transfer between compartments and/or individual cisternae, how strong is the evidence that they actually perform this function?
T48530 28766-28972 Sentence denotes While transport vesicles may represent the most likely mechanism to accomplish transfer between compartments and/or individual cisternae, how strong is the evidence that they actually perform this function?
TextSentencer_T163 28973-29141 Sentence denotes In intact cells, perhaps the best argument comes from the early cell-cell fusion experiments of Rothman and colleagues (Rothman et al., 1984a (Rothman et al., , 1984b .
T51224 28973-29141 Sentence denotes In intact cells, perhaps the best argument comes from the early cell-cell fusion experiments of Rothman and colleagues (Rothman et al., 1984a (Rothman et al., , 1984b .
TextSentencer_T164 29142-29239 Sentence denotes Here, CHO cell glycosylation mutants were infected with VSV and then fused with uninfected cells.
T64988 29142-29239 Sentence denotes Here, CHO cell glycosylation mutants were infected with VSV and then fused with uninfected cells.
TextSentencer_T165 29240-29507 Sentence denotes Transfer of the VSV G protein from Golgi membranes in the infected to the uninfected cells was monitored by a glycosylation event that could be carried out by only the uninfected recipient, which was chosen to complement the glycosylation defect of the infected cell.
T40509 29240-29507 Sentence denotes Transfer of the VSV G protein from Golgi membranes in the infected to the uninfected cells was monitored by a glycosylation event that could be carried out by only the uninfected recipient, which was chosen to complement the glycosylation defect of the infected cell.
TextSentencer_T166 29508-29625 Sentence denotes These observations indicated that efficient transfer of VSV G protein occurs between spatially distinct Golgi stacks.
T32899 29508-29625 Sentence denotes These observations indicated that efficient transfer of VSV G protein occurs between spatially distinct Golgi stacks.
TextSentencer_T167 29626-29858 Sentence denotes This is most easily explained byamechanism involving VSVG proteincontaining transport vesicles that form from the infected cell Golgi, diffuse through the heterokaryon's cytosol, and fuse with Golgi membranes in the uninfected cell.
T56442 29626-29858 Sentence denotes This is most easily explained byamechanism involving VSVG proteincontaining transport vesicles that form from the infected cell Golgi, diffuse through the heterokaryon's cytosol, and fuse with Golgi membranes in the uninfected cell.
TextSentencer_T168 29859-29967 Sentence denotes Conceivably, the same transport vesicles could mediate intercisternal transport within a single Golgi stack.
T88507 29859-29967 Sentence denotes Conceivably, the same transport vesicles could mediate intercisternal transport within a single Golgi stack.
TextSentencer_T169 29968-30029 Sentence denotes The major limitation of these data is that they are indirect.
T75405 29968-30029 Sentence denotes The major limitation of these data is that they are indirect.
TextSentencer_T170 30030-30118 Sentence denotes They do not identify the vesicles nor do they definitely establish their site of origin.
T36107 30030-30118 Sentence denotes They do not identify the vesicles nor do they definitely establish their site of origin.
TextSentencer_T171 30119-30308 Sentence denotes One cannot exclude the possibility that the G protein moved by lateral diffusion through tubules connecting the heterologous Golgi stacks, which otherwise remain separated during the assay.
T98085 30119-30308 Sentence denotes One cannot exclude the possibility that the G protein moved by lateral diffusion through tubules connecting the heterologous Golgi stacks, which otherwise remain separated during the assay.
TextSentencer_T172 30309-30536 Sentence denotes Furthermore, even the existence of vesicles involved in inter-Golgi transport does not demonstrate that they have a similar role in intercisternal transport within a single stack, as is assumed by our current view of the Golgi.
T81060 30309-30536 Sentence denotes Furthermore, even the existence of vesicles involved in inter-Golgi transport does not demonstrate that they have a similar role in intercisternal transport within a single stack, as is assumed by our current view of the Golgi.
TextSentencer_T173 30537-30783 Sentence denotes In Vitro Transport through the Golgi and the Role of Carrier Vesicles The most extensive series of considerations favoring the role of transport vesicles in intra-Golgi transport comes from experiments designed to reconstitute transport in vitro.
T35687 30537-30783 Sentence denotes In Vitro Transport through the Golgi and the Role of Carrier Vesicles The most extensive series of considerations favoring the role of transport vesicles in intra-Golgi transport comes from experiments designed to reconstitute transport in vitro.
TextSentencer_T174 30784-30918 Sentence denotes That such transport can be achieved has been demonstrated over the past several years by the pioneering work of Rothman and coworkers.
T14933 30784-30918 Sentence denotes That such transport can be achieved has been demonstrated over the past several years by the pioneering work of Rothman and coworkers.
TextSentencer_T175 30919-31124 Sentence denotes In their approach, Golgi fractions prepared from VSV-infected GlcNAc transferase-deficient 158 cells ("donor Golgi") are incubated with similar fractions from uninfected wild-type cells ('acceptor Golgi").
T62537 30919-31124 Sentence denotes In their approach, Golgi fractions prepared from VSV-infected GlcNAc transferase-deficient 158 cells ("donor Golgi") are incubated with similar fractions from uninfected wild-type cells ('acceptor Golgi").
TextSentencer_T176 31125-31395 Sentence denotes Upon the addition of ATP and cytosolderived factors, there is a progressive appearance of [3H]GlcNAc-labeled (Balch et al., 1984) and endo H-resistant (Fries and Rothman, 1981) VSV G protein, reflecting its transfer from mutant "donor" to wild-type "acceptor" membranes.
T9481 31125-31395 Sentence denotes Upon the addition of ATP and cytosolderived factors, there is a progressive appearance of [3H]GlcNAc-labeled (Balch et al., 1984) and endo H-resistant (Fries and Rothman, 1981) VSV G protein, reflecting its transfer from mutant "donor" to wild-type "acceptor" membranes.
TextSentencer_T177 31396-31669 Sentence denotes This transfer has also been dissected kinetically into two major stages: an early stage presumed to correlate with the budding of transport vesicles from the donor Golgi, and a late stage reflecting the docking and subsequent fusion of the vesicles with the acceptor Golgi.
T65485 31396-31669 Sentence denotes This transfer has also been dissected kinetically into two major stages: an early stage presumed to correlate with the budding of transport vesicles from the donor Golgi, and a late stage reflecting the docking and subsequent fusion of the vesicles with the acceptor Golgi.
TextSentencer_T178 31670-31804 Sentence denotes The early and late stages also differ in their requirements and inhibitor sensitivities (Balch et al., 1984; Rothman and Orci, 1990) .
T29613 31670-31804 Sentence denotes The early and late stages also differ in their requirements and inhibitor sensitivities (Balch et al., 1984; Rothman and Orci, 1990) .
TextSentencer_T179 31805-32166 Sentence denotes Given that VSV G protein in early Golgi compartments was transported with the highest efficiency (Fries and Rothman, 1981) the transport event assayed was postulated to reflect the formation of vesicles from cis (early) cisternae and the fusion of these vesicles with medial cisternae (which contain the GlcNAc transferase) (Rothman and Orci, 1990) (Figure 4) .
T87053 31805-32166 Sentence denotes Given that VSV G protein in early Golgi compartments was transported with the highest efficiency (Fries and Rothman, 1981) the transport event assayed was postulated to reflect the formation of vesicles from cis (early) cisternae and the fusion of these vesicles with medial cisternae (which contain the GlcNAc transferase) (Rothman and Orci, 1990) (Figure 4) .
TextSentencer_T180 32167-32212 Sentence denotes However, the identi-DONOR ACCEPTOR Fllgure 4.
T85173 32167-32212 Sentence denotes However, the identi-DONOR ACCEPTOR Fllgure 4.
TextSentencer_T181 32213-32432 Sentence denotes Two Models to Account for Donor-Acceptor Connections in Inter-Golgi Transport In Vitro (A) Vesicular transport, as predicted by the current view of the Golgi alid by the work of Rothman and colleagues (Rothman and Orci.
T66310 32213-32432 Sentence denotes Two Models to Account for Donor-Acceptor Connections in Inter-Golgi Transport In Vitro (A) Vesicular transport, as predicted by the current view of the Golgi alid by the work of Rothman and colleagues (Rothman and Orci.
TextSentencer_T182 32433-32599 Sentence denotes 1990) . (ES) Vesicle-independent direct fusions between donor and acceptor compartments (CGN-CGN, medial-medial, and TGN-TGN), perhaps mediated by tubular extensions.
T30214 32433-32599 Sentence denotes 1990) . (ES) Vesicle-independent direct fusions between donor and acceptor compartments (CGN-CGN, medial-medial, and TGN-TGN), perhaps mediated by tubular extensions.
TextSentencer_T183 32600-33017 Sentence denotes While these tubules may be amplified by BFA. as described in the text, they may exist and function even in the absence of the drug. ties of the donor and acceptor cisternae have not yet been established, nor can kinetic analysis alone provide a unique interpretation, especially when transport is monitored indirectly by linkage to glycosylation, which itself is a kinetically complex series of reactions (see above).
T63070 32600-33017 Sentence denotes While these tubules may be amplified by BFA. as described in the text, they may exist and function even in the absence of the drug. ties of the donor and acceptor cisternae have not yet been established, nor can kinetic analysis alone provide a unique interpretation, especially when transport is monitored indirectly by linkage to glycosylation, which itself is a kinetically complex series of reactions (see above).
TextSentencer_T184 33018-33205 Sentence denotes Analysis of this Golgi transport system has already led to the discovery of several discrete protein factors whose a.ctivities are required to mediate the assay (Rothman and Orci, 1990) .
T17778 33018-33205 Sentence denotes Analysis of this Golgi transport system has already led to the discovery of several discrete protein factors whose a.ctivities are required to mediate the assay (Rothman and Orci, 1990) .
TextSentencer_T185 33206-33375 Sentence denotes Some of these represent the mammalian homologs of yeast genes known to be involved in intracellular transport in intact cells (Wilson et al., 1989; Clary et al., 1990) .
T87831 33206-33375 Sentence denotes Some of these represent the mammalian homologs of yeast genes known to be involved in intracellular transport in intact cells (Wilson et al., 1989; Clary et al., 1990) .
TextSentencer_T186 33376-33751 Sentence denotes One important factor, designated NSF (NEM-.sensitive fusion protein), is homologous to the yeast sec78 gene product and is thought to act at a late stage in transport, at the time when transport vesicles fuse with the acceptor membranes Orci et al., 1989; Rexach and Schekman, 1991) both in ER to Golgi and in Golgi as well as in post-Golgi transport (Graham and Emr, 1991) .
T5937 33376-33751 Sentence denotes One important factor, designated NSF (NEM-.sensitive fusion protein), is homologous to the yeast sec78 gene product and is thought to act at a late stage in transport, at the time when transport vesicles fuse with the acceptor membranes Orci et al., 1989; Rexach and Schekman, 1991) both in ER to Golgi and in Golgi as well as in post-Golgi transport (Graham and Emr, 1991) .
TextSentencer_T187 33752-33806 Sentence denotes The precise function of NSF, however, remains unknown.
T96485 33752-33806 Sentence denotes The precise function of NSF, however, remains unknown.
TextSentencer_T188 33807-34003 Sentence denotes Another factor, designated SNAP (for soluble NSF attachment protein), is homologous to the yeast sec77 gene product and is thought to be involved in NSF binding to membranes (Clary et al., 1990) .
T56697 33807-34003 Sentence denotes Another factor, designated SNAP (for soluble NSF attachment protein), is homologous to the yeast sec77 gene product and is thought to be involved in NSF binding to membranes (Clary et al., 1990) .
TextSentencer_T189 34004-34206 Sentence denotes The strongest evidence for the existence of a vesicular intermediate in the in vitro transport reaction has been provided by the identification and isolation of the presumed carrier vesicles themselves.
T55740 34004-34206 Sentence denotes The strongest evidence for the existence of a vesicular intermediate in the in vitro transport reaction has been provided by the identification and isolation of the presumed carrier vesicles themselves.
TextSentencer_T190 34207-34350 Sentence denotes During the early stagesof the reaction, isolated Golgi membranes generate an array of coated tubules, buds, and vesicles (Orci et al., '1986 ).
T65289 34207-34350 Sentence denotes During the early stagesof the reaction, isolated Golgi membranes generate an array of coated tubules, buds, and vesicles (Orci et al., '1986 ).
TextSentencer_T191 34351-34516 Sentence denotes The vesicles have been isolated (after elution from l:heir membrane-bound state by high salt), and their coats have been found to contain several unique components .
T91579 34351-34516 Sentence denotes The vesicles have been isolated (after elution from l:heir membrane-bound state by high salt), and their coats have been found to contain several unique components .
TextSentencer_T192 34517-34722 Sentence denotes One of these, B-COP, was previously identified by Kreis and coworkers as a 110 kd peripheral protein tightly associated with the Golgi (Allan and IKreis, 1986; Duden et al., 1991b; Serafini et al., 1991) .
T16465 34517-34722 Sentence denotes One of these, B-COP, was previously identified by Kreis and coworkers as a 110 kd peripheral protein tightly associated with the Golgi (Allan and IKreis, 1986; Duden et al., 1991b; Serafini et al., 1991) .
TextSentencer_T193 34723-34800 Sentence denotes These non-clathrin-coated vesicles are good candidates ,for carrier vesicles.
T96379 34723-34800 Sentence denotes These non-clathrin-coated vesicles are good candidates ,for carrier vesicles.
TextSentencer_T194 34801-34911 Sentence denotes First, they contain VSV G protein, the iprotein being transported (Orci et al., 1986 Serafini let al., 1991) .
T49666 34801-34911 Sentence denotes First, they contain VSV G protein, the iprotein being transported (Orci et al., 1986 Serafini let al., 1991) .
TextSentencer_T195 34912-35035 Sentence denotes Next, conditions that block the transport reac-tion in general result in the accumulation or lack of formation of vesicles.
T76765 34912-35035 Sentence denotes Next, conditions that block the transport reac-tion in general result in the accumulation or lack of formation of vesicles.
TextSentencer_T196 35036-35274 Sentence denotes Most interestingly, treatment of cells or isolated membranes with the nonhydrolyzable GTP analog, GTPyS, both blocks glycosylation of the VSV G protein and results in the accumulation of VSV G protein-containing coated buds and vesicles .
T82159 35036-35274 Sentence denotes Most interestingly, treatment of cells or isolated membranes with the nonhydrolyzable GTP analog, GTPyS, both blocks glycosylation of the VSV G protein and results in the accumulation of VSV G protein-containing coated buds and vesicles .
TextSentencer_T197 35275-35384 Sentence denotes Similar results were obtained using AIF4, an inhibitor of conventional GTP-binding "G proteins" Kahn, 1991) .
T909 35275-35384 Sentence denotes Similar results were obtained using AIF4, an inhibitor of conventional GTP-binding "G proteins" Kahn, 1991) .
TextSentencer_T198 35385-35469 Sentence denotes The stage at which these inhibitors act remains unknown (Donaldson et al., 1991 b) .
T14352 35385-35469 Sentence denotes The stage at which these inhibitors act remains unknown (Donaldson et al., 1991 b) .
TextSentencer_T199 35470-35694 Sentence denotes In spite of this large amount of correlative evidence, additional data will be required before it is certain that the coated vesicles serve as unique and obligatory transport intermediates either in vitro or in intact cells.
T3523 35470-35694 Sentence denotes In spite of this large amount of correlative evidence, additional data will be required before it is certain that the coated vesicles serve as unique and obligatory transport intermediates either in vitro or in intact cells.
TextSentencer_T200 35695-35853 Sentence denotes Perhaps the most important piece of missing information pertains to whether the vesicles have a composition consistent with their presumed transport function.
T27485 35695-35853 Sentence denotes Perhaps the most important piece of missing information pertains to whether the vesicles have a composition consistent with their presumed transport function.
TextSentencer_T201 35854-36021 Sentence denotes For example, it will be important to confirm that the Golgi vesicles do not contain resident proteins, e.g., glycosyltransferases, that are not intended for transport.
T86951 35854-36021 Sentence denotes For example, it will be important to confirm that the Golgi vesicles do not contain resident proteins, e.g., glycosyltransferases, that are not intended for transport.
TextSentencer_T202 36022-36107 Sentence denotes The analogous point is well established for plasma membrane clathrin-coated vesicles.
T57013 36022-36107 Sentence denotes The analogous point is well established for plasma membrane clathrin-coated vesicles.
TextSentencer_T203 36108-36327 Sentence denotes Many examples are known where proteins destined for coated vesicle-mediated endocytosis accumulate at coated pits, while those that are not efficiently internalized do not enter coated pits (Pearse and Robinson, 1990) .
T93082 36108-36327 Sentence denotes Many examples are known where proteins destined for coated vesicle-mediated endocytosis accumulate at coated pits, while those that are not efficiently internalized do not enter coated pits (Pearse and Robinson, 1990) .
TextSentencer_T204 36328-36549 Sentence denotes Another critical unknown is a demonstration that the Golgi coated vesicles are functional in vitro, i.e., that VSV G protein-containing vesicle fractions can be used to reconstitute transport when added to acceptor Golgi.
T4291 36328-36549 Sentence denotes Another critical unknown is a demonstration that the Golgi coated vesicles are functional in vitro, i.e., that VSV G protein-containing vesicle fractions can be used to reconstitute transport when added to acceptor Golgi.
TextSentencer_T205 36550-36762 Sentence denotes The analogous experiment has recently been accomplished for a less well-characterized vesicle fraction that mediates transport from the ER to the Golgi in yeast (Groesch et al., 1990; Rexach and Schekman, 1991) .
T71691 36550-36762 Sentence denotes The analogous experiment has recently been accomplished for a less well-characterized vesicle fraction that mediates transport from the ER to the Golgi in yeast (Groesch et al., 1990; Rexach and Schekman, 1991) .
TextSentencer_T206 36763-36816 Sentence denotes Thus, in principle, this approach should be possible.
T89315 36763-36816 Sentence denotes Thus, in principle, this approach should be possible.
TextSentencer_T207 36817-36986 Sentence denotes However, with all such experiments, it will be important to ensure that the coated vesicle fractions used are not contaminated with uncoated, fusion-competent membranes.
T37511 36817-36986 Sentence denotes However, with all such experiments, it will be important to ensure that the coated vesicle fractions used are not contaminated with uncoated, fusion-competent membranes.
TextSentencer_T208 36987-37273 Sentence denotes BFA Blocks Vesicle Formation without Blocking Transport A reason for examining the features of the Golgi vesicles so carefully is indicated by a recent paper that raises the possibility that, at least under certain conditions, these vesicles may not be required for transport in vitro .
T22722 36987-37273 Sentence denotes BFA Blocks Vesicle Formation without Blocking Transport A reason for examining the features of the Golgi vesicles so carefully is indicated by a recent paper that raises the possibility that, at least under certain conditions, these vesicles may not be required for transport in vitro .
TextSentencer_T209 37274-37350 Sentence denotes In this work, the effect of BFA on the Golgi transport assay was determined.
T9149 37274-37350 Sentence denotes In this work, the effect of BFA on the Golgi transport assay was determined.
TextSentencer_T210 37351-37520 Sentence denotes BFA is a macrocyclic fungal antibiotic that blocks the transport of membrane and secretory proteins through the Golgi (Takatsuki and Tamura, 1985; Misumi et al., 1986) .
T64782 37351-37520 Sentence denotes BFA is a macrocyclic fungal antibiotic that blocks the transport of membrane and secretory proteins through the Golgi (Takatsuki and Tamura, 1985; Misumi et al., 1986) .
TextSentencer_T211 37521-37703 Sentence denotes In intact cells, the drug causes a dramatic and rapid retrograde transport of Golgi components back to the ER via a system of tubular extensions (Lippincott- Schwartz et al., 1990) .
T833 37521-37703 Sentence denotes In intact cells, the drug causes a dramatic and rapid retrograde transport of Golgi components back to the ER via a system of tubular extensions (Lippincott- Schwartz et al., 1990) .
TextSentencer_T212 37704-37899 Sentence denotes The mechanism of BFA action is unknown, but one intriguing property is its ability to rapidly, and reversibly, trigger the dissociation of B-COP (Donaldson et al., 1991a; Klausner et al., 1992) .
T52943 37704-37899 Sentence denotes The mechanism of BFA action is unknown, but one intriguing property is its ability to rapidly, and reversibly, trigger the dissociation of B-COP (Donaldson et al., 1991a; Klausner et al., 1992) .
TextSentencer_T213 37900-38039 Sentence denotes When isolated Golgi was treated with BFA, P-COP was no longer associated with the membranes nor were any coated buds or vesicles detected .
T76917 37900-38039 Sentence denotes When isolated Golgi was treated with BFA, P-COP was no longer associated with the membranes nor were any coated buds or vesicles detected .
TextSentencer_T214 38040-38185 Sentence denotes Nevertheless, the transfer of VSV G protein from donor to acceptor Golgi continued with similar kinetics and efficiency as in untreated controls.
T98539 38040-38185 Sentence denotes Nevertheless, the transfer of VSV G protein from donor to acceptor Golgi continued with similar kinetics and efficiency as in untreated controls.
TextSentencer_T215 38186-38286 Sentence denotes The only difference was that transfer in BFA-treated Golgi lost its sensitivity to GTPyS inhibition.
T70150 38186-38286 Sentence denotes The only difference was that transfer in BFA-treated Golgi lost its sensitivity to GTPyS inhibition.
TextSentencer_T216 38287-38343 Sentence denotes There are two possible interpretations of these results.
T66058 38287-38343 Sentence denotes There are two possible interpretations of these results.
TextSentencer_T217 38344-38497 Sentence denotes The first is that coated vesicles that form in the assay system are not obligatory intermediates in the transport event, even in the absence of the drug.
T81019 38344-38497 Sentence denotes The first is that coated vesicles that form in the assay system are not obligatory intermediates in the transport event, even in the absence of the drug.
TextSentencer_T218 38498-38665 Sentence denotes Alternatively, BFA may induce an aberrant form of transport that nevertheless utilizes enzymatic machinery required for vesicular transport in the absence of the drug.
T86162 38498-38665 Sentence denotes Alternatively, BFA may induce an aberrant form of transport that nevertheless utilizes enzymatic machinery required for vesicular transport in the absence of the drug.
TextSentencer_T219 38666-38741 Sentence denotes It is at present impossible to distinguish between these two possibilities.
T12955 38666-38741 Sentence denotes It is at present impossible to distinguish between these two possibilities.
TextSentencer_T220 38742-38949 Sentence denotes However, BFA-treated Golgi in vitro appear to form tubular extensions that may serve to interconnect donor and acceptor Golgi stacks, thus resulting in transfer to the acceptor across these tubular bridges .
T16163 38742-38949 Sentence denotes However, BFA-treated Golgi in vitro appear to form tubular extensions that may serve to interconnect donor and acceptor Golgi stacks, thus resulting in transfer to the acceptor across these tubular bridges .
TextSentencer_T221 38950-39064 Sentence denotes This possibility is appealing since it could reflect the BFA-induced tubulation of the Golgi seen in intact cells.
T73446 38950-39064 Sentence denotes This possibility is appealing since it could reflect the BFA-induced tubulation of the Golgi seen in intact cells.
TextSentencer_T222 39065-39229 Sentence denotes However, additional electron microscope immunocytochemistry will be required to establish continuous interconnections between antigenically distinct Golgi elements.
T7104 39065-39229 Sentence denotes However, additional electron microscope immunocytochemistry will be required to establish continuous interconnections between antigenically distinct Golgi elements.
TextSentencer_T223 39230-39266 Sentence denotes Vesicular Transport or Golgi Fusion?
T85620 39230-39266 Sentence denotes Vesicular Transport or Golgi Fusion?
TextSentencer_T224 39267-39410 Sentence denotes The fact that "transport" (i.e., G protein glycosylation) can occur in the absence of vesicle formation raises a number of important questions:
T64972 39267-39410 Sentence denotes The fact that "transport" (i.e., G protein glycosylation) can occur in the absence of vesicle formation raises a number of important questions:
TextSentencer_T225 39411-39470 Sentence denotes What transport step(s) is actually being measured in vitro?
T87995 39411-39470 Sentence denotes What transport step(s) is actually being measured in vitro?
TextSentencer_T226 39471-39564 Sentence denotes What is the relationship of the events reconstituted in vitro to those found in intact cells?
T63093 39471-39564 Sentence denotes What is the relationship of the events reconstituted in vitro to those found in intact cells?
TextSentencer_T227 39565-39662 Sentence denotes Is transport in vitro ever completely dependent on vesicle formation, even in the absence of BFA?
T1878 39565-39662 Sentence denotes Is transport in vitro ever completely dependent on vesicle formation, even in the absence of BFA?
TextSentencer_T228 39663-39792 Sentence denotes If vesicles are not involved, is transfer from donor to acceptor Golgi mediated by direct fusion, perhaps via tubular extensions?
T5069 39663-39792 Sentence denotes If vesicles are not involved, is transfer from donor to acceptor Golgi mediated by direct fusion, perhaps via tubular extensions?
TextSentencer_T229 39793-40000 Sentence denotes As mentioned above, it is unclear whether the G protein is transferred across a predicted compartment boundary (donor CGN to acceptor medial) or within a single compartment (donor medial to acceptor medial).
T79243 39793-40000 Sentence denotes As mentioned above, it is unclear whether the G protein is transferred across a predicted compartment boundary (donor CGN to acceptor medial) or within a single compartment (donor medial to acceptor medial).
TextSentencer_T230 40001-40163 Sentence denotes It is becoming increasingly clear that all membranebound organelles have a propensity to form tubules in intact cells and in vitro, with or without BFA treatment.
T55949 40001-40163 Sentence denotes It is becoming increasingly clear that all membranebound organelles have a propensity to form tubules in intact cells and in vitro, with or without BFA treatment.
TextSentencer_T231 40164-40536 Sentence denotes For example, the ER (Lee and Chen, 1988), mitochondria (Johnson et al., 1980) peroxisomes (Yamamoto and Fahimi, 1987) endosomes (Hopkins et al., 1990; Tooze and Hollinshead, 1991; Hunziker et al., 1991b; Lippincott-Schwartz et al., 1991) , and lysosomes (Swanson et al., 1987; Lippincott-Schwartz et al., 1991) are all capable of forming dynamic tubular membrane networks.
T84435 40164-40536 Sentence denotes For example, the ER (Lee and Chen, 1988), mitochondria (Johnson et al., 1980) peroxisomes (Yamamoto and Fahimi, 1987) endosomes (Hopkins et al., 1990; Tooze and Hollinshead, 1991; Hunziker et al., 1991b; Lippincott-Schwartz et al., 1991) , and lysosomes (Swanson et al., 1987; Lippincott-Schwartz et al., 1991) are all capable of forming dynamic tubular membrane networks.
TextSentencer_T232 40537-40680 Sentence denotes One wellstudied example is the early endosome, the structure of which varies in different cell types (Marsh et al., 1986; Tooze et al., 1991) .
T7767 40537-40680 Sentence denotes One wellstudied example is the early endosome, the structure of which varies in different cell types (Marsh et al., 1986; Tooze et al., 1991) .
TextSentencer_T233 40681-40809 Sentence denotes Cell-free assays have documented that the early endosome elements can fuse avidly with each other (Gruenberg and Howell, 1989) .
T45511 40681-40809 Sentence denotes Cell-free assays have documented that the early endosome elements can fuse avidly with each other (Gruenberg and Howell, 1989) .
TextSentencer_T234 40810-40991 Sentence denotes Other examples of processes involving homotypic fusion in vitro are the assembly of the nuclear envelope (Burke and Gerace, 1986) and the formation of ER (Dabora and Sheetz, 1988) .
T33785 40810-40991 Sentence denotes Other examples of processes involving homotypic fusion in vitro are the assembly of the nuclear envelope (Burke and Gerace, 1986) and the formation of ER (Dabora and Sheetz, 1988) .
TextSentencer_T235 40992-41215 Sentence denotes The Golgi complex is also a dynamic structure that can be disassembled by microtubule depolymerization into fragments that remain functional despite being dispersed throughout the cytoplasm (Thyberg and Moskalewski, 1985) .
T72467 40992-41215 Sentence denotes The Golgi complex is also a dynamic structure that can be disassembled by microtubule depolymerization into fragments that remain functional despite being dispersed throughout the cytoplasm (Thyberg and Moskalewski, 1985) .
TextSentencer_T236 41216-41358 Sentence denotes Upon microtubule reassembly, the Golgi fragments rapidly reassemble and assume their characteristic cisternal organization (Ho et al., 1989) .
T27386 41216-41358 Sentence denotes Upon microtubule reassembly, the Golgi fragments rapidly reassemble and assume their characteristic cisternal organization (Ho et al., 1989) .
TextSentencer_T237 41359-41507 Sentence denotes A similar series of events must occur during mitosis when the Golgi fragments into populations of small vesicles and tubules (Lucocq et al., 1989) .
T43149 41359-41507 Sentence denotes A similar series of events must occur during mitosis when the Golgi fragments into populations of small vesicles and tubules (Lucocq et al., 1989) .
TextSentencer_T238 41508-41553 Sentence denotes During telophase, these fragments reassemble.
T24552 41508-41553 Sentence denotes During telophase, these fragments reassemble.
TextSentencer_T239 41554-41837 Sentence denotes Given that homotypic fusion occurs so commonly, it would be premature to dismiss the possibility that the intra-Golgi transport activity observed in vitro actually reflects a process of regulated tubule formation and/or direct fusion of donor and acceptor Golgi elements (Figure 4) .
T85700 41554-41837 Sentence denotes Given that homotypic fusion occurs so commonly, it would be premature to dismiss the possibility that the intra-Golgi transport activity observed in vitro actually reflects a process of regulated tubule formation and/or direct fusion of donor and acceptor Golgi elements (Figure 4) .
TextSentencer_T240 41838-42084 Sentence denotes Indeed, even in untreated Golgi, both in vitro and in intact cells, tubules can be found that are similar to those observed in BFA-treated Golgi (Hermo et al., 1980; Braell et al., 1984 [see Figure 8b in this reference]; Griffiths et al., 1985) .
T55764 41838-42084 Sentence denotes Indeed, even in untreated Golgi, both in vitro and in intact cells, tubules can be found that are similar to those observed in BFA-treated Golgi (Hermo et al., 1980; Braell et al., 1984 [see Figure 8b in this reference]; Griffiths et al., 1985) .
TextSentencer_T241 42085-42285 Sentence denotes That a direct fusion event is possible is also suggested by the fact that the predicted diffusion coefficient of intact Golgi stacks is ~1 O-fold less than that of the much smaller coated vesicles (N.
T99333 42085-42285 Sentence denotes That a direct fusion event is possible is also suggested by the fact that the predicted diffusion coefficient of intact Golgi stacks is ~1 O-fold less than that of the much smaller coated vesicles (N.
TextSentencer_T242 42286-42315 Sentence denotes Ktistakis, unpublished data).
T7812 42286-42315 Sentence denotes Ktistakis, unpublished data).
TextSentencer_T243 42316-42575 Sentence denotes Thus, one might expect a decrease in the kinetics of VSV G protein transfer if BFA were to switch the signal generated in vitro from a vesicle-dependent phenomenon (as is presumed to occur in the absence of the drug) to a direct, tubule-mediated fusion event.
T5759 42316-42575 Sentence denotes Thus, one might expect a decrease in the kinetics of VSV G protein transfer if BFA were to switch the signal generated in vitro from a vesicle-dependent phenomenon (as is presumed to occur in the absence of the drug) to a direct, tubule-mediated fusion event.
TextSentencer_T244 42576-42691 Sentence denotes However, G protein is transported from donor to acceptor with the same kinetics in the presence or absence of BFA .
T79305 42576-42691 Sentence denotes However, G protein is transported from donor to acceptor with the same kinetics in the presence or absence of BFA .
TextSentencer_T245 42692-43014 Sentence denotes Finally, the fact that the two N-linked chains of VSV G protein are processed simultaneously in vitro as opposed to sequentially in permeabilized cells may also indicate that compartmental boundaries may not be strictly preserved, i.e., that direct fusion may occur, during the cell-free assay (Schwaninger et al., 1991) .
T2914 42692-43014 Sentence denotes Finally, the fact that the two N-linked chains of VSV G protein are processed simultaneously in vitro as opposed to sequentially in permeabilized cells may also indicate that compartmental boundaries may not be strictly preserved, i.e., that direct fusion may occur, during the cell-free assay (Schwaninger et al., 1991) .
TextSentencer_T246 43015-43219 Sentence denotes The minimal model that we discussed (see Figure 3 ) predicts only two functional and presumably physical discontinuities in theGolgi: from theCGN to the medial Golgi, and from the medial Golgi to the TGN.
T29291 43015-43219 Sentence denotes The minimal model that we discussed (see Figure 3 ) predicts only two functional and presumably physical discontinuities in theGolgi: from theCGN to the medial Golgi, and from the medial Golgi to the TGN.
TextSentencer_T247 43220-43449 Sentence denotes Thus, according to this view, transport through the Golgi involves two intercompartmental transfers, reflecting transfer from the site of entry to the site of glycosylation, and from the site of glycosylation to the site of exit.
T7819 43220-43449 Sentence denotes Thus, according to this view, transport through the Golgi involves two intercompartmental transfers, reflecting transfer from the site of entry to the site of glycosylation, and from the site of glycosylation to the site of exit.
TextSentencer_T248 43450-43868 Sentence denotes Considering available data, we consider it likely that the intercompartmental transfers between CGNlmedial and medial/TGN boundaries occur in vivo via vesicular carriers While the putative transporters remain to be identified, the P-COP-containing vesicles Serafini et al., 1991) are obvious but unconfirmed candidates, whether or not they are ultimately found to function as carrier vesicles in in vitro Golgi assays.
T67688 43450-43868 Sentence denotes Considering available data, we consider it likely that the intercompartmental transfers between CGNlmedial and medial/TGN boundaries occur in vivo via vesicular carriers While the putative transporters remain to be identified, the P-COP-containing vesicles Serafini et al., 1991) are obvious but unconfirmed candidates, whether or not they are ultimately found to function as carrier vesicles in in vitro Golgi assays.
TextSentencer_T249 43869-44183 Sentence denotes The tubular interconnections known to occur in the Golgi may also play a role in intercompartmental transfer, but we view these as probably being more important for establishing and maintaining intracompartmental links that serve to interconnect functionally identical Golgi compartments and to mix their contents.
T81285 43869-44183 Sentence denotes The tubular interconnections known to occur in the Golgi may also play a role in intercompartmental transfer, but we view these as probably being more important for establishing and maintaining intracompartmental links that serve to interconnect functionally identical Golgi compartments and to mix their contents.
TextSentencer_T250 44184-44345 Sentence denotes These tubular connections may break and fuse continuously, accounting for the dynamic behavior of the Golgi complex after microtubule disassembly and reassembly.
T74080 44184-44345 Sentence denotes These tubular connections may break and fuse continuously, accounting for the dynamic behavior of the Golgi complex after microtubule disassembly and reassembly.
TextSentencer_T251 44346-44550 Sentence denotes However, if their formation is tightly controlled by a regulated process of assembly and disassembly of the f&COP-containing Golgi coat, even tubule-based intercompartmental transfer is not inconceivable.
T32975 44346-44550 Sentence denotes However, if their formation is tightly controlled by a regulated process of assembly and disassembly of the f&COP-containing Golgi coat, even tubule-based intercompartmental transfer is not inconceivable.
TextSentencer_T252 44551-44737 Sentence denotes Moreover, whether cell-free assays of Golgi function reflect such an intercompartmental transfer, or intracompartmental transfer between wild-type and mutant Golgi, remains to be solved.
T12404 44551-44737 Sentence denotes Moreover, whether cell-free assays of Golgi function reflect such an intercompartmental transfer, or intracompartmental transfer between wild-type and mutant Golgi, remains to be solved.
TextSentencer_T253 44738-44867 Sentence denotes Only further characterization of the machinery responsible for intra-Golgi transport will decide between these two possibilities.
T55089 44738-44867 Sentence denotes Only further characterization of the machinery responsible for intra-Golgi transport will decide between these two possibilities.
TextSentencer_T254 44868-45159 Sentence denotes Nevertheless, based on the evidence both from the in vitro assays and from yeast genetics, it is clear that the few proteins identified thus far, such as NSF and SNAP, are generally important elements, irrespective of the precise pathways or whether transport occurs via vesicles or tubules.
T89504 44868-45159 Sentence denotes Nevertheless, based on the evidence both from the in vitro assays and from yeast genetics, it is clear that the few proteins identified thus far, such as NSF and SNAP, are generally important elements, irrespective of the precise pathways or whether transport occurs via vesicles or tubules.
TextSentencer_T255 45160-45217 Sentence denotes Is Transport through the Golgi Selective or Nonselective?
T33110 45160-45217 Sentence denotes Is Transport through the Golgi Selective or Nonselective?
TextSentencer_T256 45218-45556 Sentence denotes Having considered the evidence for the compartmental organization of the Golgi and for the role of carrier vesicles in transport, we come to the last of the three general elements underlying our view of Golgi function, namely, that transport of passenger proteins through the Golgi is inherently nonselective (Pfeffer and Rothman, 1987) .
T81144 45218-45556 Sentence denotes Having considered the evidence for the compartmental organization of the Golgi and for the role of carrier vesicles in transport, we come to the last of the three general elements underlying our view of Golgi function, namely, that transport of passenger proteins through the Golgi is inherently nonselective (Pfeffer and Rothman, 1987) .
TextSentencer_T257 45557-45746 Sentence denotes The evidence for this view is largely indirect or negative, in that efforts to identify discrete signals on proteins that are required for forward transport have thus far been unsuccessful.
T48502 45557-45746 Sentence denotes The evidence for this view is largely indirect or negative, in that efforts to identify discrete signals on proteins that are required for forward transport have thus far been unsuccessful.
TextSentencer_T258 45747-46046 Sentence denotes On the other hand, as discussed above, there is now considerable evidence in favor of several distinct "retenlion signals" that effectively prevent forward transport of membrane or lumenal proteins after reaching their prescribed destinations in the ER or various Golgi compartments (Pelham, 1991) .
T49988 45747-46046 Sentence denotes On the other hand, as discussed above, there is now considerable evidence in favor of several distinct "retenlion signals" that effectively prevent forward transport of membrane or lumenal proteins after reaching their prescribed destinations in the ER or various Golgi compartments (Pelham, 1991) .
TextSentencer_T259 46047-46242 Sentence denotes If this view is correct, selectivity in I.ransport through the secretory pathway may occur by "default," i.e., transport of passenger proteins proceeds owing to the absence of a retention signal.
T42367 46047-46242 Sentence denotes If this view is correct, selectivity in I.ransport through the secretory pathway may occur by "default," i.e., transport of passenger proteins proceeds owing to the absence of a retention signal.
TextSentencer_T260 46243-46360 Sentence denotes This concept, however, is not necessarily incompatible with the existence of selective signals for forward transport.
T73379 46243-46360 Sentence denotes This concept, however, is not necessarily incompatible with the existence of selective signals for forward transport.
TextSentencer_T261 46361-46483 Sentence denotes It is clear that such signals exist and play an important role in directing the traffic of proteins as they leave the TGN.
T22273 46361-46483 Sentence denotes It is clear that such signals exist and play an important role in directing the traffic of proteins as they leave the TGN.
TextSentencer_T262 46484-46796 Sentence denotes Examples include the mannose g-phosphate residues that specify transport of hydrolytic enzymes to lysosomes and Mellman, 1989) and the cytoplasmic domain determiinants that target newly synthesized membrane proteins to ithe basolateral surface of polarized cells (Hunziker et al., 1991a; Brewer and Roth, 1991) .
T23340 46484-46796 Sentence denotes Examples include the mannose g-phosphate residues that specify transport of hydrolytic enzymes to lysosomes and Mellman, 1989) and the cytoplasmic domain determiinants that target newly synthesized membrane proteins to ithe basolateral surface of polarized cells (Hunziker et al., 1991a; Brewer and Roth, 1991) .
TextSentencer_T263 46797-47250 Sentence denotes Since the transport of ,fluorescent lipids from the Golgi to the plasma membrane Iin nonpolarized cells occurs very rapidly, it is thought that "constitutive" transport from the Golgi to the cell surface may not require specific signals . ,Analogous results were obtained in experiments in which a tripeptide containing a cognate site for N-linked glycosylation presumably also involved transport from the ER (Wieland et al., 1987; Helms et al., 1990) .
T19968 46797-47250 Sentence denotes Since the transport of ,fluorescent lipids from the Golgi to the plasma membrane Iin nonpolarized cells occurs very rapidly, it is thought that "constitutive" transport from the Golgi to the cell surface may not require specific signals . ,Analogous results were obtained in experiments in which a tripeptide containing a cognate site for N-linked glycosylation presumably also involved transport from the ER (Wieland et al., 1987; Helms et al., 1990) .
TextSentencer_T264 47251-47434 Sentence denotes While these experiments suggest that signals are not necessary for transport, the fact that they are released with rapid kinetics does not alone establish the absence of such signals.
T80947 47251-47434 Sentence denotes While these experiments suggest that signals are not necessary for transport, the fact that they are released with rapid kinetics does not alone establish the absence of such signals.
TextSentencer_T265 47435-47652 Sentence denotes Experiments showing that different secretory and membrane proteins are transported with different kinetics may indicate that signals or receptors are involved in forward transport (Lodish et al., 1983; Lodish, 1988) .
T75773 47435-47652 Sentence denotes Experiments showing that different secretory and membrane proteins are transported with different kinetics may indicate that signals or receptors are involved in forward transport (Lodish et al., 1983; Lodish, 1988) .
TextSentencer_T266 47653-47906 Sentence denotes Similarly, the suggestion that newly synthesized viral spike glycoproteins are present in Golgi membranes at a density severalfold greater than in the ER is also consistent with the existence of signal-driven forward transport (Griffiths et al., 1984) .
T67488 47653-47906 Sentence denotes Similarly, the suggestion that newly synthesized viral spike glycoproteins are present in Golgi membranes at a density severalfold greater than in the ER is also consistent with the existence of signal-driven forward transport (Griffiths et al., 1984) .
TextSentencer_T267 47907-48011 Sentence denotes However, both of these observations might also be reconciled with a nonselective mechanism of transport.
T16023 47907-48011 Sentence denotes However, both of these observations might also be reconciled with a nonselective mechanism of transport.
TextSentencer_T268 48012-48201 Sentence denotes Given recent evidence that exit from the ER is linked to the folding of newly synthesized proteins, differential folding rates among proteins may indirectly affect their transport kinetics.
T83032 48012-48201 Sentence denotes Given recent evidence that exit from the ER is linked to the folding of newly synthesized proteins, differential folding rates among proteins may indirectly affect their transport kinetics.
TextSentencer_T269 48202-48416 Sentence denotes Moreover, if the intrinsic rate of transport of glycoproteins through the Golgi is slow relative to the rate of ER exit, then one might also expect a higher concentration of certain passenger proteins in the Golgi.
T90132 48202-48416 Sentence denotes Moreover, if the intrinsic rate of transport of glycoproteins through the Golgi is slow relative to the rate of ER exit, then one might also expect a higher concentration of certain passenger proteins in the Golgi.
TextSentencer_T270 48417-48540 Sentence denotes At present, most of the attention paid to the question of signals in transport concerns ER to Golgi or postQolgi transport.
T96026 48417-48540 Sentence denotes At present, most of the attention paid to the question of signals in transport concerns ER to Golgi or postQolgi transport.
TextSentencer_T271 48541-48647 Sentence denotes Whether transport through the Golgi complex itself is selective or nonselective is still an open question.
T13403 48541-48647 Sentence denotes Whether transport through the Golgi complex itself is selective or nonselective is still an open question.
TextSentencer_T272 48648-48740 Sentence denotes After years of descriptive work, the Golgi complex is slowly starting to reveal its secrets.
T32151 48648-48740 Sentence denotes After years of descriptive work, the Golgi complex is slowly starting to reveal its secrets.
TextSentencer_T273 48741-48937 Sentence denotes We have now entered an exciting period of research, during which it will become possible to define the molecular mechanisms responsible for generating and maintaining Golgi structure and function.
T47790 48741-48937 Sentence denotes We have now entered an exciting period of research, during which it will become possible to define the molecular mechanisms responsible for generating and maintaining Golgi structure and function.
TextSentencer_T274 48938-49268 Sentence denotes The first phase is already well under way and has been characterized by a search for essential bits and pieces of the Golgi machinery, a number of which have already been found (NSFlsecl8, aSNAPlsecl7, (J-COP, ARF[Stearnsetal., 19901, rab6p[Goudetal., 1990] ,sec7p [Achstetter et al., 19881, and secl4p [Bankaitis et al., 199Oj) .
T91727 48938-49268 Sentence denotes The first phase is already well under way and has been characterized by a search for essential bits and pieces of the Golgi machinery, a number of which have already been found (NSFlsecl8, aSNAPlsecl7, (J-COP, ARF[Stearnsetal., 19901, rab6p[Goudetal., 1990] ,sec7p [Achstetter et al., 19881, and secl4p [Bankaitis et al., 199Oj) .
TextSentencer_T275 49269-49394 Sentence denotes As we have seen, however, it is at present difficult to know precisely what steps are controlled by each of these components.
T63538 49269-49394 Sentence denotes As we have seen, however, it is at present difficult to know precisely what steps are controlled by each of these components.
TextSentencer_T276 49395-49597 Sentence denotes Nevertheless, the observed conservation of Golgi proteins between S. cerevisiae and mammals is most encouraging for our ability to confirm in living cells the function of components identified in vitro.
T1842 49395-49597 Sentence denotes Nevertheless, the observed conservation of Golgi proteins between S. cerevisiae and mammals is most encouraging for our ability to confirm in living cells the function of components identified in vitro.
TextSentencer_T277 49598-49670 Sentence denotes The combination of cell-free analysis and genetics has proven its worth.
T96610 49598-49670 Sentence denotes The combination of cell-free analysis and genetics has proven its worth.
TextSentencer_T278 49671-49740 Sentence denotes The next phase will have to deal with the questions that have arisen.
T9340 49671-49740 Sentence denotes The next phase will have to deal with the questions that have arisen.
TextSentencer_T279 49741-49779 Sentence denotes How many Golgi compartments are there?
T25976 49741-49779 Sentence denotes How many Golgi compartments are there?
TextSentencer_T280 49780-49846 Sentence denotes Are compartment boundaries defined by specific protein frameworks?
T37846 49780-49846 Sentence denotes Are compartment boundaries defined by specific protein frameworks?
TextSentencer_T281 49847-49902 Sentence denotes If so, how do they function and how are they regulated?
T11232 49847-49902 Sentence denotes If so, how do they function and how are they regulated?
TextSentencer_T282 49903-49972 Sentence denotes Does transport between Golgi compartments require vesicular carriers?
T72127 49903-49972 Sentence denotes Does transport between Golgi compartments require vesicular carriers?
TextSentencer_T283 49973-50001 Sentence denotes What is the role of tubules?
T62431 49973-50001 Sentence denotes What is the role of tubules?
TextSentencer_T284 50002-50110 Sentence denotes How does the machinery responsible for forward traffic relate to the machinery controlling homotypic fusion?
T42934 50002-50110 Sentence denotes How does the machinery responsible for forward traffic relate to the machinery controlling homotypic fusion?
TextSentencer_T285 50111-50172 Sentence denotes How is specificity of forward and backward traffic regulated?
T37675 50111-50172 Sentence denotes How is specificity of forward and backward traffic regulated?
TextSentencer_T286 50173-50234 Sentence denotes How does lipid composition and organization affect transport?
T6350 50173-50234 Sentence denotes How does lipid composition and organization affect transport?
TextSentencer_T287 50235-50279 Sentence denotes What function does the stack structure have?
T14190 50235-50279 Sentence denotes What function does the stack structure have?
TextSentencer_T288 50280-50333 Sentence denotes How do microtubules interact with the Golgi elements?
T46028 50280-50333 Sentence denotes How do microtubules interact with the Golgi elements?
TextSentencer_T289 50334-50464 Sentence denotes The challenge will be to integrate the information we are now collecting in the context of how the Golgi complex works as a whole.
T69741 50334-50464 Sentence denotes The challenge will be to integrate the information we are now collecting in the context of how the Golgi complex works as a whole.