CORVET and HOPS tethering complexes–coordinators of endosome and lysosome fusion

Abstract

SummaryProtein and lipid transport along the endolysosomal system of eukaryotic cells depends on multiple fusion and fission events. Over the past few years, the molecular constituents of both fission and fusion machineries have been identified. Here, we focus on the mechanism of membrane fusion at endosomes, vacuoles and lysosomes, and in particular on the role of the two homologous tethering complexes called CORVET and HOPS. Both complexes are heterohexamers; they share four subunits, interact with Rab GTPases and soluble NSF attachment protein receptors (SNAREs) and can tether membranes. Owing to the presence of specific subunits, CORVET is a Rab5 effector complex, whereas HOPS can bind efficiently to late endosomes and lysosomes through Rab7. Based on the recently described overall structure of the HOPS complex and a number of in vivo and in vitro analyses, important insights into their function have been obtained. Here, we discuss the general function of both complexes in yeast and in metazoan cells in the context of endosomal biogenesis and maturation.

AtVPS41-mediated endocytic pathway is essential for pollen tube–stigma interaction inArabidopsis

“…In yeast cells, the HOPS complex is recruited by the active form of RAB GTPase Ypt7/RAB7 to mediate fusion between the prevacuolar compartment membrane and vacuole/lysosome membrane with the assistance of SNARE proteins (16)(17)(18). In Arabidopsis, RAB7/RABG GTPases and a Rab5 homolog Rha1/RABF2a were also involved in vacuolar trafficking of cargo proteins (24)(25)(26).…”

“…In yeast, studies on vacuolar assembly identified a tethering complex, the homotypic fusion and vacuolar protein sorting (HOPS) complex, which consists of four core subunits and two HOPS-specific subunits, Vps41p and Vps39p (15). Vps41p promotes membrane fusion between late endosomes and lysosomes by working as an effector of Ypt7, a GTP-binding protein (16)(17)(18). Loss of Vps41p function led to failure of vacuole membrane fusion and production of fragmented vacuoles (19).…”

Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity

“…17,18 CORVET promotes the maturation of early to late endosomes in yeast but remains poorly characterized in animals. Metazoan HOPS and CORVET tethering complexes are speculated to share 5 subunits: the homologs of CG32350/Vps11, Vps16, dor/Vps18, car/Vps33, and Vps39.…”

“…Metazoan HOPS and CORVET tethering complexes are speculated to share 5 subunits: the homologs of CG32350/Vps11, Vps16, dor/Vps18, car/Vps33, and Vps39. 17,18 We have recently shown that autophagosomes accumulate when any one of the 6 HOPS subunits are lost in Drosophila, and the levels of both lipidated and nonlipidated forms of Atg8a and ref(2)P/p62 are massively upregulated not only in Vps16A-null mutants but also in hypomorphic CG32350/Vps11-or lt/Vps41-mutant animals. 11,19 Importantly, CG32350/Vps11-mutant larvae also developed slower than control animals, which could be again partially rescued by the expression of Rheb (Fig.…”

“…17,18 Two additional subunits specify HOPS (Vps39, lt/Vps41) and CORVET (Vps3, CG10144/Vps8) in this unicellular eukaryote, respectively, although intermediate complexes may also exist. Mutations in genes encoding C-Vps subunits are synthetic lethal with tor1 mutations (note that there are 2 different genes encoding Tor in yeast, and it is Tor1 that is part of Tor complex 1), and C-Vps mutants are hypersensitive to rapamycin, suggesting a role for this complex in Tor complex 1 signaling.…”