Show simple item record

Defects in COG-Mediated Golgi Trafficking Alter Endo-Lysosoma System in Human Cells

dc.contributor.authorD'Souza, Zinia
dc.contributor.authorBlackburn, Jessica Bailey
dc.contributor.authorKudlyk, Tetyana
dc.contributor.authorPokrovskaya, Irina
dc.contributor.authorLupashin, Vladimir V.
dc.date.accessioned2019-10-08T20:07:02Z
dc.date.available2019-10-08T20:07:02Z
dc.date.issued2019-07-03
dc.identifier.citationD’Souza Z, Blackburn JB, Kudlyk T, Pokrovskaya ID and Lupashin VV (2019) Defects in COG-Mediated Golgi Trafficking Alter Endo-Lysosomal System in Human Cells. Front. Cell Dev. Biol. 7:118. doi: 10.3389/fcell.2019.00118en_US
dc.identifier.issn2296-634X
dc.identifier.urihttp://hdl.handle.net/1803/9575
dc.description.abstractThe conserved oligomeric complex (COG) is a multi-subunit vesicle tethering complex that functions in retrograde trafficking at the Golgi. We have previously demonstrated that the formation of enlarged endo-lysosomal structures (EELSs) is one of the major glycosylation-independent phenotypes of cells depleted for individual COG complex subunits. Here, we characterize the EELSs in HEK293T cells using microscopy and biochemical approaches. Our analysis revealed that the EELSs are highly acidic and that vATPase-dependent acidification is essential for the maintenance of this enlarged compartment. The EELSs are accessible to both trans-Golgi enzymes and endocytic cargo. Moreover, the EELSs specifically accumulate endolysosomal proteins Lamp2, CD63, Rab7, Rab9, Rab39, Vamp7, and STX8 on their surface. The EELSs are distinct from lysosomes and do not accumulate active Cathepsin B. Retention using selective hooks (RUSH) experiments revealed that biosynthetic cargo mCherry-Lampl reaches the EELSs much faster as compared to both receptor-mediated and soluble endocytic cargo, indicating TGN origin of the EELSs. In support to this hypothesis, EELSs are enriched with TGN specific lipid PI4P. Additionally, analysis of COG4/VPS54 double KO cells revealed that the activity of the GARP tethering complex is necessary for EELSs' accumulation, indicating that protein mistargeting and the imbalance of Golgi-endosome membrane flow leads to the formation of EELSs in COG-deficient cells. The EELSs are likely to serve as a degradative storage hybrid organelle for mistargeted Golgi enzymes and underglycosylated glycoconjugates. To our knowledge this is the first report of the formation of an enlarged hybrid endosomal compartment in a response to malfunction of the intra-Golgi trafficking machinery.en_US
dc.description.sponsorshipThis work was supported by the National Institutes of Health (R01GM083144) (VL).en_US
dc.language.isoen_USen_US
dc.publisherFRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGYen_US
dc.rightsCopyright © 2019 D’Souza, Blackburn, Kudlyk, Pokrovskaya and Lupashin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Frontiers
dc.source.urihttps://www.frontiersin.org/articles/10.3389/fcell.2019.00118/full
dc.subjectCOG complexen_US
dc.subjectgolgi apparatusen_US
dc.subjectCRISPRen_US
dc.subjectendosomesen_US
dc.subjectglycosyltransferaseen_US
dc.subjectGARP complexen_US
dc.subjectendocytosisen_US
dc.subjectconserved oligomeric golgien_US
dc.subjectcongenital disorderen_US
dc.subjecttethering factorsen_US
dc.subjectmembrane-proteinen_US
dc.subjectSNARE complexesen_US
dc.subjectplasma-membraneen_US
dc.subjectV-atpaesen_US
dc.subjectH+Atpaseen_US
dc.subjectglycosylationen_US
dc.subjectdeficiencyen_US
dc.subject.lcshGolgi apparatusen_US
dc.subject.lcshEndocytosisen_US
dc.titleDefects in COG-Mediated Golgi Trafficking Alter Endo-Lysosoma System in Human Cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fcell.2019.00118


Files in this item

Icon

This item appears in the following Collection(s)

Show simple item record