Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt
| Autor: | Ágnes Varga, Viktória Kiss, Lili Anna Kenéz, Sarolta Tóth, Tamás Csizmadia, Zsófia Simon-Vecsei, Gábor Juhász, Péter Lőrincz |
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| Rok vydání: | 2019 |
| Předmět: |
crinophagy
autophagy CORVET QH301-705.5 Endosome Science Endocytic cycle Vesicular Transport Proteins Gene Expression Endosomes Endocytosis General Biochemistry Genetics and Molecular Biology Organelle Animals Drosophila Proteins endocytosis Biology (General) Late endosome HOPS General Immunology and Microbiology D. melanogaster Chemistry General Neuroscience Vesicle Autophagy General Medicine Cell Biology Cell biology Drosophila melanogaster Medicine tethering Research Advance Biogenesis Developmental Biology |
| Zdroj: | eLife eLife, Vol 8 (2019) |
| ISSN: | 2050-084X |
| Popis: | Two related multisubunit tethering complexes promote endolysosomal trafficking in all eukaryotes: Rab5-binding CORVET that was suggested to transform into Rab7-binding HOPS. We have previously identified miniCORVET, containing Drosophila Vps8 and three shared core proteins, which are required for endosome maturation upstream of HOPS in highly endocytic cells (Lőrincz et al., 2016a). Here, we show that Vps8 overexpression inhibits HOPS-dependent trafficking routes including late endosome maturation, autophagosome-lysosome fusion, crinophagy and lysosome-related organelle formation. Mechanistically, Vps8 overexpression abolishes the late endosomal localization of HOPS-specific Vps41/Lt and prevents HOPS assembly. Proper ratio of Vps8 to Vps41 is thus critical because Vps8 negatively regulates HOPS by outcompeting Vps41. Endosomal recruitment of miniCORVET- or HOPS-specific subunits requires proper complex assembly, and Vps8/miniCORVET is dispensable for autophagy, crinophagy and lysosomal biogenesis. These data together indicate the recruitment of these complexes to target membranes independent of each other in Drosophila, rather than their transformation during vesicle maturation. |
| Databáze: | OpenAIRE |
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