PMC:6194691 / 71194-72845 JSONTXT

{"project":"MyTest","denotations":[{"id":"30340614-11238745-30706198","span":{"begin":453,"end":455},"obj":"11238745"},{"id":"30340614-3694713-30706199","span":{"begin":457,"end":460},"obj":"3694713"},{"id":"30340614-3224280-30706200","span":{"begin":650,"end":652},"obj":"3224280"},{"id":"30340614-1450923-30706201","span":{"begin":654,"end":657},"obj":"1450923"},{"id":"30340614-9593852-30706202","span":{"begin":659,"end":662},"obj":"9593852"},{"id":"30340614-14580938-30706203","span":{"begin":853,"end":856},"obj":"14580938"},{"id":"30340614-25315861-30706204","span":{"begin":1599,"end":1602},"obj":"25315861"},{"id":"30340614-26687231-30706204","span":{"begin":1599,"end":1602},"obj":"26687231"},{"id":"30340614-29054412-30706204","span":{"begin":1599,"end":1602},"obj":"29054412"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Transport of transferrin is closely related to transfer of iron. Iron in plasma and in brain extracellular fluid is present almost entirely complexed to transferrin i.e. as holo-transferrin. It has long been known that iron and transferrin enter the brain across the blood–brain barrier and it was originally hypothesised that they are transferred together by endocytosis followed by exocytosis, i.e. direct transcytosis, of holo-transferrin (see e.g. [61, 276]). Yet there have been arguments against this idea arising from dual labelling experiments showing that far more labelled iron than labelled transferrin accumulates in the brain, see e.g. [60, 277, 278]. In addition it has been argued that release of holo-transferrin from TfR is unlikely to occur as there needs to be prior dissociation of iron for release of transferrin from its receptor [279]. So though there is general agreement that holo-transferrin interacts with TfR, which then mediates endocytosis of the iron/transferrin/receptor complex into the endothelial cells, there has been controversy over the subsequent steps in the transfers of transferrin and iron into the brain. Assuming that holo-transferrin is indeed directly transcytosed across the blood–brain barrier, then the limited net entry observed of transferrin to the brain implies that there must be transcytosis of transferrin without iron, apo-transferrin, back out of the brain. Alternatively if the iron is dissociated from the transferrin within the endothelial cells, it is likely that there is exocytosis of apo-transferrin on both sides of the cells (see [280–282] and the footnote13 for further discussion)."}

{"project":"2_test","denotations":[{"id":"30340614-11238745-30706198","span":{"begin":453,"end":455},"obj":"11238745"},{"id":"30340614-3694713-30706199","span":{"begin":457,"end":460},"obj":"3694713"},{"id":"30340614-3224280-30706200","span":{"begin":650,"end":652},"obj":"3224280"},{"id":"30340614-1450923-30706201","span":{"begin":654,"end":657},"obj":"1450923"},{"id":"30340614-9593852-30706202","span":{"begin":659,"end":662},"obj":"9593852"},{"id":"30340614-14580938-30706203","span":{"begin":853,"end":856},"obj":"14580938"},{"id":"30340614-25315861-30706204","span":{"begin":1599,"end":1602},"obj":"25315861"},{"id":"30340614-26687231-30706204","span":{"begin":1599,"end":1602},"obj":"26687231"},{"id":"30340614-29054412-30706204","span":{"begin":1599,"end":1602},"obj":"29054412"}],"text":"Transport of transferrin is closely related to transfer of iron. Iron in plasma and in brain extracellular fluid is present almost entirely complexed to transferrin i.e. as holo-transferrin. It has long been known that iron and transferrin enter the brain across the blood–brain barrier and it was originally hypothesised that they are transferred together by endocytosis followed by exocytosis, i.e. direct transcytosis, of holo-transferrin (see e.g. [61, 276]). Yet there have been arguments against this idea arising from dual labelling experiments showing that far more labelled iron than labelled transferrin accumulates in the brain, see e.g. [60, 277, 278]. In addition it has been argued that release of holo-transferrin from TfR is unlikely to occur as there needs to be prior dissociation of iron for release of transferrin from its receptor [279]. So though there is general agreement that holo-transferrin interacts with TfR, which then mediates endocytosis of the iron/transferrin/receptor complex into the endothelial cells, there has been controversy over the subsequent steps in the transfers of transferrin and iron into the brain. Assuming that holo-transferrin is indeed directly transcytosed across the blood–brain barrier, then the limited net entry observed of transferrin to the brain implies that there must be transcytosis of transferrin without iron, apo-transferrin, back out of the brain. Alternatively if the iron is dissociated from the transferrin within the endothelial cells, it is likely that there is exocytosis of apo-transferrin on both sides of the cells (see [280–282] and the footnote13 for further discussion)."}