PubMed:17435236
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/17435236","sourcedb":"PubMed","sourceid":"17435236","text":"Genetic modifiers of the Drosophila blue cheese gene link defects in lysosomal transport with decreased life span and altered ubiquitinated-protein profiles.\nDefects in lysosomal trafficking pathways lead to decreased cell viability and are associated with progressive disorders in humans. Previously we have found that loss-of-function (LOF) mutations in the Drosophila gene blue cheese (bchs) lead to reduced adult life span, increased neuronal death, and widespread CNS degeneration that is associated with the formation of ubiquitinated-protein aggregates. To identify potential genes that participate in the bchs functional pathway, we conducted a genetic modifier screen based on alterations of an eye phenotype that arises from high-level overexpression of Bchs. We found that mutations in select autophagic and endocytic trafficking genes, defects in cytoskeletal and motor proteins, as well as mutations in the SUMO and ubiquitin signaling pathways behave as modifiers of the Bchs gain-of-function (GOF) eye phenotype. Individual mutant alleles that produced viable adults were further examined for bchs-like phenotypes. Mutations in several lysosomal trafficking genes resulted in significantly decreased adult life spans and several mutants showed changes in ubiquitinated protein profiles as young adults. This work represents a novel approach to examine the role that lysosomal transport and function have on adult viability. The genes characterized in this study have direct human homologs, suggesting that similar defects in lysosomal transport may play a role in human health and age-related processes.","tracks":[{"project":"sonoma2","denotations":[{"id":"T0","span":{"begin":8,"end":17},"obj":"VAR"},{"id":"T1","span":{"begin":36,"end":47},"obj":"GENE"},{"id":"T2","span":{"begin":58,"end":65},"obj":"VAR"},{"id":"T3","span":{"begin":94,"end":103},"obj":"NEGREG"},{"id":"T4","span":{"begin":118,"end":125},"obj":"REG"},{"id":"T5","span":{"begin":126,"end":156},"obj":"MPA"},{"id":"T6","span":{"begin":158,"end":165},"obj":"VAR"},{"id":"T7","span":{"begin":200,"end":204},"obj":"REG"},{"id":"T8","span":{"begin":208,"end":217},"obj":"NEGREG"},{"id":"T9","span":{"begin":223,"end":232},"obj":"CPA"},{"id":"T10","span":{"begin":241,"end":251},"obj":"REG"},{"id":"T11","span":{"begin":257,"end":278},"obj":"DISEASE"},{"id":"T12","span":{"begin":269,"end":278},"obj":"DISEASE"},{"id":"T13","span":{"begin":320,"end":336},"obj":"NEGREG"},{"id":"T14","span":{"begin":338,"end":341},"obj":"NEGREG"},{"id":"T15","span":{"begin":343,"end":352},"obj":"VAR"},{"id":"T16","span":{"begin":376,"end":387},"obj":"GENE"},{"id":"T17","span":{"begin":389,"end":393},"obj":"GENE"},{"id":"T18","span":{"begin":403,"end":410},"obj":"NEGREG"},{"id":"T19","span":{"begin":411,"end":421},"obj":"CPA"},{"id":"T20","span":{"begin":417,"end":426},"obj":"CPA"},{"id":"T21","span":{"begin":428,"end":437},"obj":"POSREG"},{"id":"T22","span":{"begin":438,"end":452},"obj":"DISEASE"},{"id":"T23","span":{"begin":447,"end":452},"obj":"CPA"},{"id":"T24","span":{"begin":469,"end":485},"obj":"CPA"},{"id":"T25","span":{"begin":469,"end":485},"obj":"DISEASE"},{"id":"T26","span":{"begin":494,"end":504},"obj":"REG"},{"id":"T27","span":{"begin":527,"end":559},"obj":"MPA"},{"id":"T28","span":{"begin":613,"end":617},"obj":"GENE"},{"id":"T29","span":{"begin":686,"end":697},"obj":"REG"},{"id":"T30","span":{"begin":764,"end":768},"obj":"GENE"},{"id":"T31","span":{"begin":784,"end":793},"obj":"VAR"},{"id":"T32","span":{"begin":848,"end":855},"obj":"VAR"},{"id":"T33","span":{"begin":903,"end":912},"obj":"VAR"},{"id":"T34","span":{"begin":968,"end":977},"obj":"REG"},{"id":"T35","span":{"begin":985,"end":989},"obj":"GENE"},{"id":"T36","span":{"begin":990,"end":1006},"obj":"POSREG"},{"id":"T37","span":{"begin":1008,"end":1011},"obj":"POSREG"},{"id":"T38","span":{"begin":1013,"end":1016},"obj":"CPA"},{"id":"T39","span":{"begin":1039,"end":1053},"obj":"VAR"},{"id":"T40","span":{"begin":1108,"end":1117},"obj":"GENE"},{"id":"T41","span":{"begin":1130,"end":1139},"obj":"VAR"},{"id":"T42","span":{"begin":1205,"end":1214},"obj":"NEGREG"},{"id":"T43","span":{"begin":1244,"end":1251},"obj":"VAR"},{"id":"T44","span":{"begin":1259,"end":1266},"obj":"REG"},{"id":"T45","span":{"begin":1270,"end":1300},"obj":"MPA"},{"id":"T46","span":{"begin":1529,"end":1536},"obj":"VAR"},{"id":"T47","span":{"begin":1571,"end":1575},"obj":"REG"}],"relations":[{"id":"R0","pred":"CauseOf","subj":"T2","obj":"T3"},{"id":"R1","pred":"CauseOf","subj":"T2","obj":"T4"},{"id":"R2","pred":"ThemeOf","subj":"T5","obj":"T4"},{"id":"R3","pred":"CauseOf","subj":"T6","obj":"T7"},{"id":"R4","pred":"CauseOf","subj":"T6","obj":"T8"},{"id":"R5","pred":"CauseOf","subj":"T6","obj":"T10"},{"id":"R6","pred":"ThemeOf","subj":"T9","obj":"T8"},{"id":"R7","pred":"ThemeOf","subj":"T12","obj":"T8"},{"id":"R8","pred":"ThemeOf","subj":"T12","obj":"T10"},{"id":"R9","pred":"CauseOf","subj":"T14","obj":"T13"},{"id":"R21","pred":"ThemeOf","subj":"T20","obj":"T18"},{"id":"R22","pred":"ThemeOf","subj":"T23","obj":"T21"},{"id":"R23","pred":"ThemeOf","subj":"T24","obj":"T13"},{"id":"R24","pred":"ThemeOf","subj":"T24","obj":"T26"},{"id":"R25","pred":"CauseOf","subj":"T31","obj":"T34"},{"id":"R26","pred":"CauseOf","subj":"T31","obj":"T36"},{"id":"R27","pred":"CauseOf","subj":"T31","obj":"T37"},{"id":"R28","pred":"CauseOf","subj":"T32","obj":"T34"},{"id":"R29","pred":"CauseOf","subj":"T32","obj":"T36"},{"id":"R30","pred":"CauseOf","subj":"T32","obj":"T37"},{"id":"R31","pred":"CauseOf","subj":"T33","obj":"T34"},{"id":"R32","pred":"CauseOf","subj":"T33","obj":"T36"},{"id":"R10","pred":"CauseOf","subj":"T13","obj":"T18"},{"id":"R11","pred":"CauseOf","subj":"T13","obj":"T21"},{"id":"R12","pred":"CauseOf","subj":"T14","obj":"T18"},{"id":"R13","pred":"CauseOf","subj":"T14","obj":"T21"},{"id":"R14","pred":"CauseOf","subj":"T15","obj":"T13"},{"id":"R15","pred":"CauseOf","subj":"T15","obj":"T14"},{"id":"R16","pred":"CauseOf","subj":"T15","obj":"T18"},{"id":"R17","pred":"CauseOf","subj":"T15","obj":"T21"},{"id":"R18","pred":"ThemeOf","subj":"T17","obj":"T15"},{"id":"R19","pred":"ThemeOf","subj":"T19","obj":"T18"},{"id":"R20","pred":"ThemeOf","subj":"T20","obj":"T13"},{"id":"R33","pred":"CauseOf","subj":"T33","obj":"T37"},{"id":"R34","pred":"CauseOf","subj":"T34","obj":"T36"},{"id":"R35","pred":"ThemeOf","subj":"T35","obj":"T34"},{"id":"R36","pred":"CauseOf","subj":"T37","obj":"T36"},{"id":"R37","pred":"ThemeOf","subj":"T38","obj":"T34"},{"id":"R38","pred":"ThemeOf","subj":"T38","obj":"T36"},{"id":"R39","pred":"ThemeOf","subj":"T38","obj":"T37"},{"id":"R40","pred":"CauseOf","subj":"T41","obj":"T42"},{"id":"R41","pred":"CauseOf","subj":"T41","obj":"T44"},{"id":"R42","pred":"CauseOf","subj":"T43","obj":"T42"},{"id":"R43","pred":"CauseOf","subj":"T43","obj":"T44"},{"id":"R44","pred":"ThemeOf","subj":"T45","obj":"T44"},{"id":"R45","pred":"CauseOf","subj":"T46","obj":"T47"}],"attributes":[{"subj":"T0","pred":"source","obj":"sonoma2"},{"subj":"T1","pred":"source","obj":"sonoma2"},{"subj":"T2","pred":"source","obj":"sonoma2"},{"subj":"T3","pred":"source","obj":"sonoma2"},{"subj":"T4","pred":"source","obj":"sonoma2"},{"subj":"T5","pred":"source","obj":"sonoma2"},{"subj":"T6","pred":"source","obj":"sonoma2"},{"subj":"T7","pred":"source","obj":"sonoma2"},{"subj":"T8","pred":"source","obj":"sonoma2"},{"subj":"T9","pred":"source","obj":"sonoma2"},{"subj":"T10","pred":"source","obj":"sonoma2"},{"subj":"T11","pred":"source","obj":"sonoma2"},{"subj":"T12","pred":"source","obj":"sonoma2"},{"subj":"T13","pred":"source","obj":"sonoma2"},{"subj":"T14","pred":"source","obj":"sonoma2"},{"subj":"T15","pred":"source","obj":"sonoma2"},{"subj":"T16","pred":"source","obj":"sonoma2"},{"subj":"T17","pred":"source","obj":"sonoma2"},{"subj":"T18","pred":"source","obj":"sonoma2"},{"subj":"T19","pred":"source","obj":"sonoma2"},{"subj":"T20","pred":"source","obj":"sonoma2"},{"subj":"T21","pred":"source","obj":"sonoma2"},{"subj":"T22","pred":"source","obj":"sonoma2"},{"subj":"T23","pred":"source","obj":"sonoma2"},{"subj":"T24","pred":"source","obj":"sonoma2"},{"subj":"T25","pred":"source","obj":"sonoma2"},{"subj":"T26","pred":"source","obj":"sonoma2"},{"subj":"T27","pred":"source","obj":"sonoma2"},{"subj":"T28","pred":"source","obj":"sonoma2"},{"subj":"T29","pred":"source","obj":"sonoma2"},{"subj":"T30","pred":"source","obj":"sonoma2"},{"subj":"T31","pred":"source","obj":"sonoma2"},{"subj":"T32","pred":"source","obj":"sonoma2"},{"subj":"T33","pred":"source","obj":"sonoma2"},{"subj":"T34","pred":"source","obj":"sonoma2"},{"subj":"T35","pred":"source","obj":"sonoma2"},{"subj":"T36","pred":"source","obj":"sonoma2"},{"subj":"T37","pred":"source","obj":"sonoma2"},{"subj":"T38","pred":"source","obj":"sonoma2"},{"subj":"T39","pred":"source","obj":"sonoma2"},{"subj":"T40","pred":"source","obj":"sonoma2"},{"subj":"T41","pred":"source","obj":"sonoma2"},{"subj":"T42","pred":"source","obj":"sonoma2"},{"subj":"T43","pred":"source","obj":"sonoma2"},{"subj":"T44","pred":"source","obj":"sonoma2"},{"subj":"T45","pred":"source","obj":"sonoma2"},{"subj":"T46","pred":"source","obj":"sonoma2"},{"subj":"T47","pred":"source","obj":"sonoma2"}]},{"project":"sonoma","denotations":[{"id":"T-0","span":{"begin":343,"end":352},"obj":"VAR"},{"id":"T-1","span":{"begin":389,"end":393},"obj":"GENE"},{"id":"T-2","span":{"begin":403,"end":410},"obj":"NEGREG"},{"id":"T-3","span":{"begin":411,"end":426},"obj":"CPA"},{"id":"T-4","span":{"begin":428,"end":437},"obj":"POSREG"},{"id":"T-5","span":{"begin":438,"end":452},"obj":"CPA"},{"id":"T-6","span":{"begin":458,"end":472},"obj":"CPA"},{"id":"T-7","span":{"begin":473,"end":485},"obj":"NEGREG"},{"id":"T-8","span":{"begin":1130,"end":1139},"obj":"VAR"},{"id":"T-9","span":{"begin":1151,"end":1178},"obj":"GENE"},{"id":"T-10","span":{"begin":1205,"end":1214},"obj":"NEGREG"},{"id":"T-11","span":{"begin":1215,"end":1231},"obj":"CPA"},{"id":"T-12","span":{"begin":1259,"end":1266},"obj":"REG"},{"id":"T-13","span":{"begin":1270,"end":1300},"obj":"MPA"}],"relations":[{"id":"R-0","pred":"ThemeOf","subj":"T-1","obj":"T-0"},{"id":"R-1","pred":"ThemeOf","subj":"T-13","obj":"T-12"},{"id":"R-2","pred":"CauseOf","subj":"T-0","obj":"T-2"},{"id":"R-3","pred":"CauseOf","subj":"T-0","obj":"T-4"},{"id":"R-4","pred":"CauseOf","subj":"T-0","obj":"T-7"},{"id":"R-5","pred":"ThemeOf","subj":"T-3","obj":"T-2"},{"id":"R-6","pred":"ThemeOf","subj":"T-5","obj":"T-4"},{"id":"R-7","pred":"ThemeOf","subj":"T-6","obj":"T-7"},{"id":"R-8","pred":"ThemeOf","subj":"T-9","obj":"T-8"},{"id":"R-9","pred":"CauseOf","subj":"T-8","obj":"T-10"},{"id":"R-10","pred":"CauseOf","subj":"T-8","obj":"T-12"},{"id":"R-11","pred":"ThemeOf","subj":"T-11","obj":"T-10"}],"attributes":[{"subj":"T-0","pred":"source","obj":"sonoma"},{"subj":"T-1","pred":"source","obj":"sonoma"},{"subj":"T-2","pred":"source","obj":"sonoma"},{"subj":"T-3","pred":"source","obj":"sonoma"},{"subj":"T-4","pred":"source","obj":"sonoma"},{"subj":"T-5","pred":"source","obj":"sonoma"},{"subj":"T-6","pred":"source","obj":"sonoma"},{"subj":"T-7","pred":"source","obj":"sonoma"},{"subj":"T-8","pred":"source","obj":"sonoma"},{"subj":"T-9","pred":"source","obj":"sonoma"},{"subj":"T-10","pred":"source","obj":"sonoma"},{"subj":"T-11","pred":"source","obj":"sonoma"},{"subj":"T-12","pred":"source","obj":"sonoma"},{"subj":"T-13","pred":"source","obj":"sonoma"}]},{"project":"kaiyin_test","denotations":[{"id":"T1","span":{"begin":343,"end":352},"obj":"Var"},{"id":"T4","span":{"begin":360,"end":387},"obj":"Gene"},{"id":"T13","span":{"begin":403,"end":410},"obj":"NegReg"},{"id":"T14","span":{"begin":411,"end":426},"obj":"CPA"},{"id":"T2","span":{"begin":428,"end":437},"obj":"PosReg"},{"id":"T3","span":{"begin":438,"end":452},"obj":"CPA"},{"id":"T6","span":{"begin":458,"end":472},"obj":"CPA"},{"id":"T5","span":{"begin":473,"end":485},"obj":"NegReg"},{"id":"T7","span":{"begin":1130,"end":1139},"obj":"Var"},{"id":"T8","span":{"begin":1151,"end":1178},"obj":"Gene"},{"id":"T9","span":{"begin":1205,"end":1214},"obj":"NegReg"},{"id":"T12","span":{"begin":1215,"end":1231},"obj":"CPA"},{"id":"T10","span":{"begin":1259,"end":1266},"obj":"Reg"},{"id":"T11","span":{"begin":1270,"end":1300},"obj":"MPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T4","obj":"T1"},{"id":"R10","pred":"ThemeOf","subj":"T11","obj":"T10"},{"id":"R11","pred":"CauseOf","subj":"T1","obj":"T13"},{"id":"R12","pred":"ThemeOf","subj":"T14","obj":"T13"},{"id":"R2","pred":"CauseOf","subj":"T1","obj":"T2"},{"id":"R3","pred":"ThemeOf","subj":"T3","obj":"T2"},{"id":"R4","pred":"CauseOf","subj":"T1","obj":"T5"},{"id":"R5","pred":"ThemeOf","subj":"T6","obj":"T5"},{"id":"R6","pred":"ThemeOf","subj":"T8","obj":"T7"},{"id":"R7","pred":"CauseOf","subj":"T7","obj":"T9"},{"id":"R8","pred":"ThemeOf","subj":"T12","obj":"T9"},{"id":"R9","pred":"CauseOf","subj":"T7","obj":"T10"}],"attributes":[{"subj":"T1","pred":"source","obj":"kaiyin_test"},{"subj":"T4","pred":"source","obj":"kaiyin_test"},{"subj":"T13","pred":"source","obj":"kaiyin_test"},{"subj":"T14","pred":"source","obj":"kaiyin_test"},{"subj":"T2","pred":"source","obj":"kaiyin_test"},{"subj":"T3","pred":"source","obj":"kaiyin_test"},{"subj":"T6","pred":"source","obj":"kaiyin_test"},{"subj":"T5","pred":"source","obj":"kaiyin_test"},{"subj":"T7","pred":"source","obj":"kaiyin_test"},{"subj":"T8","pred":"source","obj":"kaiyin_test"},{"subj":"T9","pred":"source","obj":"kaiyin_test"},{"subj":"T12","pred":"source","obj":"kaiyin_test"},{"subj":"T10","pred":"source","obj":"kaiyin_test"},{"subj":"T11","pred":"source","obj":"kaiyin_test"}]},{"project":"name_no","denotations":[{"id":"T1","span":{"begin":343,"end":352},"obj":"Var"},{"id":"T4","span":{"begin":360,"end":387},"obj":"Gene"},{"id":"T13","span":{"begin":403,"end":410},"obj":"NegReg"},{"id":"T14","span":{"begin":411,"end":426},"obj":"CPA"},{"id":"T2","span":{"begin":428,"end":437},"obj":"PosReg"},{"id":"T3","span":{"begin":438,"end":452},"obj":"CPA"},{"id":"T6","span":{"begin":458,"end":472},"obj":"CPA"},{"id":"T5","span":{"begin":473,"end":485},"obj":"NegReg"},{"id":"T7","span":{"begin":1130,"end":1139},"obj":"Var"},{"id":"T8","span":{"begin":1151,"end":1178},"obj":"Gene"},{"id":"T9","span":{"begin":1205,"end":1214},"obj":"NegReg"},{"id":"T12","span":{"begin":1215,"end":1231},"obj":"CPA"},{"id":"T10","span":{"begin":1259,"end":1266},"obj":"Reg"},{"id":"T11","span":{"begin":1270,"end":1300},"obj":"MPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T4","obj":"T1"},{"id":"R10","pred":"ThemeOf","subj":"T11","obj":"T10"},{"id":"R11","pred":"CauseOf","subj":"T1","obj":"T13"},{"id":"R12","pred":"ThemeOf","subj":"T14","obj":"T13"},{"id":"R2","pred":"CauseOf","subj":"T1","obj":"T2"},{"id":"R3","pred":"ThemeOf","subj":"T3","obj":"T2"},{"id":"R4","pred":"CauseOf","subj":"T1","obj":"T5"},{"id":"R5","pred":"ThemeOf","subj":"T6","obj":"T5"},{"id":"R6","pred":"ThemeOf","subj":"T8","obj":"T7"},{"id":"R7","pred":"CauseOf","subj":"T7","obj":"T9"},{"id":"R8","pred":"ThemeOf","subj":"T12","obj":"T9"},{"id":"R9","pred":"CauseOf","subj":"T7","obj":"T10"}],"attributes":[{"subj":"T1","pred":"source","obj":"name_no"},{"subj":"T4","pred":"source","obj":"name_no"},{"subj":"T13","pred":"source","obj":"name_no"},{"subj":"T14","pred":"source","obj":"name_no"},{"subj":"T2","pred":"source","obj":"name_no"},{"subj":"T3","pred":"source","obj":"name_no"},{"subj":"T6","pred":"source","obj":"name_no"},{"subj":"T5","pred":"source","obj":"name_no"},{"subj":"T7","pred":"source","obj":"name_no"},{"subj":"T8","pred":"source","obj":"name_no"},{"subj":"T9","pred":"source","obj":"name_no"},{"subj":"T12","pred":"source","obj":"name_no"},{"subj":"T10","pred":"source","obj":"name_no"},{"subj":"T11","pred":"source","obj":"name_no"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sonoma2","color":"#ec9c93","default":true},{"id":"sonoma","color":"#93a3ec"},{"id":"kaiyin_test","color":"#beec93"},{"id":"name_no","color":"#ec93d8"}]}]}}