TY - JOUR TI - Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt AU - Lőrincz, Péter AU - Kenéz, Lili Anna AU - Tóth, Sarolta AU - Kiss, Viktória AU - Varga, Ágnes AU - Csizmadia, Tamás AU - Simon-Vecsei, Zsófia AU - Juhász, Gábor A2 - Merz, Alexey J A2 - Malhotra, Vivek A2 - Merz, Alexey J A2 - Ungermann, Christian VL - 8 PY - 2019 DA - 2019/06/13 SP - e45631 C1 - eLife 2019;8:e45631 DO - 10.7554/eLife.45631 UR - https://doi.org/10.7554/eLife.45631 AB - 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. KW - HOPS KW - CORVET KW - autophagy KW - endocytosis KW - crinophagy KW - tethering JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -