Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pgen.1001055
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dc.titleMultivesicular body formation requires OSBP-related proteins and cholesterol
dc.contributor.authorKobuna H.
dc.contributor.authorInoue T.
dc.contributor.authorShibata M.
dc.contributor.authorGengyo-Ando K.
dc.contributor.authorYamamoto A.
dc.contributor.authorMitani S.
dc.contributor.authorArai H.
dc.date.accessioned2019-11-06T09:33:04Z
dc.date.available2019-11-06T09:33:04Z
dc.date.issued2010
dc.identifier.citationKobuna H., Inoue T., Shibata M., Gengyo-Ando K., Yamamoto A., Mitani S., Arai H. (2010). Multivesicular body formation requires OSBP-related proteins and cholesterol. PLoS Genetics 6 (8). ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pgen.1001055
dc.identifier.issn15537390
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161659
dc.description.abstractIn eukaryotes, different subcellular organelles have distinct cholesterol concentrations, which is thought to be critical for biological functions. Oxysterol-binding protein-related proteins (ORPs) have been assumed to mediate nonvesicular cholesterol trafficking in cells; however, their in vivo functions and therefore the biological significance of cholesterol in each organelle are not fully understood. Here, by generating deletion mutants of ORPs in Caenorhabditis elegans, we show that ORPs are required for the formation and function of multivesicular bodies (MVBs). In an RNAi enhancer screen using obr quadruple mutants (obr-1; -2; -3; -4), we found that MVB-related genes show strong genetic interactions with the obr genes. In obr quadruple mutants, late endosomes/lysosomes are enlarged and membrane protein degradation is retarded, although endocytosed soluble proteins are normally delivered to lysosomes and degraded. We also found that the cholesterol content of late endosomes/lysosomes is reduced in the mutants. In wild-type worms, cholesterol restriction induces the formation of enlarged late endosomes/lysosomes, as observed in obr quadruple mutants, and increases embryonic lethality upon knockdown of MVB-related genes. Finally, we show that knockdown of ORP1L, a mammalian ORP family member, induces the formation of enlarged MVBs in HeLa cells. Our in vivo findings suggest that the proper cholesterol level of late endosomes/lysosomes generated by ORPs is required for normal MVB formation and MVB-mediated membrane protein degradation. © 2010 Kobuna et al.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectcarrier protein
dc.subjectcholesterol
dc.subjectoxysterol binding protein related protein
dc.subjectunclassified drug
dc.subjectarticle
dc.subjectCaenorhabditis elegans
dc.subjectcell enlargement
dc.subjectcell organelle
dc.subjectcontrolled study
dc.subjectembryo death
dc.subjectendocytosis
dc.subjectendosome
dc.subjectgene interaction
dc.subjectHeLa cell
dc.subjecthuman
dc.subjecthuman cell
dc.subjectlysosome
dc.subjectmulltivesicular body
dc.subjectmutant
dc.subjectnonhuman
dc.subjectnucleotide sequence
dc.subjectprotein degradation
dc.subjectprotein function
dc.subjectprotein transport
dc.subjectRNA interference
dc.subjectwild type
dc.subjectAnimals
dc.subjectCaenorhabditis elegans
dc.subjectCaenorhabditis elegans Proteins
dc.subjectCholesterol
dc.subjectHela Cells
dc.subjectHumans
dc.subjectMultigene Family
dc.subjectMultivesicular Bodies
dc.subjectReceptors, Steroid
dc.subjectCaenorhabditis elegans
dc.subjectEukaryota
dc.subjectMammalia
dc.typeArticle
dc.contributor.departmentBIOCHEMISTRY
dc.description.doi10.1371/journal.pgen.1001055
dc.description.sourcetitlePLoS Genetics
dc.description.volume6
dc.description.issue8
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