VAM6

Summary

Gene Symbol: VAM6
Description: Vam6p
Alias: CVT4, VPL18, VPL22, VPS39, Vam6p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Wang L, Seeley E, Wickner W, Merz A. Vacuole fusion at a ring of vertex docking sites leaves membrane fragments within the organelle. Cell. 2002;108:357-69 pubmed
    ..Their vertex enrichment requires cis-SNARE complex disassembly and is thus part of the normal fusion pathway. ..
  2. Xu H, Wickner W. Bem1p is a positive regulator of the homotypic fusion of yeast vacuoles. J Biol Chem. 2006;281:27158-66 pubmed
    ..2005) Genes Dev. 19, 2606-2618), we did not find phosphorylation of Bem1p at Ser-72 to be required for Bem1p-stimulated fusion. Taken together, Bem1p is a positive regulator of lipid mixing during vacuole hemifusion and fusion. ..
  3. Cabrera M, Langemeyer L, Mari M, Rethmeier R, Orban I, Perz A, et al. Phosphorylation of a membrane curvature-sensing motif switches function of the HOPS subunit Vps41 in membrane tethering. J Cell Biol. 2010;191:845-59 pubmed publisher
    ..This multifunctional tethering factor thus discriminates between trafficking routes by switching from a curvature-sensing to a coat recognition mode upon phosphorylation. ..
  4. Seals D, Eitzen G, Margolis N, Wickner W, Price A. A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for homotypic vacuole fusion. Proc Natl Acad Sci U S A. 2000;97:9402-7 pubmed
    ..Vacuole-associated Vam2p and Vam6p (Vam2/6p) are components of a 65S complex containing SNARE proteins...
  5. Pieren M, Schmidt A, Mayer A. The SM protein Vps33 and the t-SNARE H(abc) domain promote fusion pore opening. Nat Struct Mol Biol. 2010;17:710-7 pubmed publisher
    ..This suggests that SM proteins promote fusion pore opening by enhancing the fusogenic activity of a SNARE complex. They should thus be considered integral parts of the fusion machinery. ..
  6. Wang C, Stromhaug P, Kauffman E, Weisman L, Klionsky D. Yeast homotypic vacuole fusion requires the Ccz1-Mon1 complex during the tethering/docking stage. J Cell Biol. 2003;163:973-85 pubmed
    ..Accordingly, we propose that the Ccz1-Mon1 complex is critical for the Ypt7-dependent tethering/docking stage leading to the formation of a trans-SNARE complex and subsequent vacuole fusion. ..
  7. Binda M, Péli Gulli M, Bonfils G, Panchaud N, Urban J, Sturgill T, et al. The Vam6 GEF controls TORC1 by activating the EGO complex. Mol Cell. 2009;35:563-73 pubmed publisher
    ..that the nucleotide-binding status of Gtr1 is regulated by the conserved guanine nucleotide exchange factor (GEF) Vam6. Thus, in addition to its regulatory role in homotypic vacuolar fusion and vacuole protein sorting within the HOPS ..
  8. Collins K, Thorngren N, Fratti R, Wickner W. Sec17p and HOPS, in distinct SNARE complexes, mediate SNARE complex disruption or assembly for fusion. EMBO J. 2005;24:1775-86 pubmed
    ..Sec17p may displace HOPS from SNAREs to permit subsequent rounds of fusion. ..
  9. Nordmann M, Cabrera M, Perz A, Bröcker C, Ostrowicz C, Engelbrecht Vandré S, et al. The Mon1-Ccz1 complex is the GEF of the late endosomal Rab7 homolog Ypt7. Curr Biol. 2010;20:1654-9 pubmed publisher
    ..Its subunit Vps39/Vam6 has been proposed as a GEF for Ypt7 [12] and the Rag GTPase Gtr1 [13], but other genetic evidence has ..

More Information

Publications36

  1. Ostrowicz C, Bröcker C, Ahnert F, Nordmann M, Lachmann J, Peplowska K, et al. Defined subunit arrangement and rab interactions are required for functionality of the HOPS tethering complex. Traffic. 2010;11:1334-46 pubmed publisher
    ..center of HOPS and CORVET, the class C proteins Vps11 and Vps18 connect the two parts, and Vps11 binds both HOPS Vps39 and CORVET Vps3 via the same binding site...
  2. Stroupe C, Collins K, Fratti R, Wickner W. Purification of active HOPS complex reveals its affinities for phosphoinositides and the SNARE Vam7p. EMBO J. 2006;25:1579-89 pubmed
    ..Concentration of the HOPS complex at these microdomains may be a key factor for coupling Rab GTPase activation to SNARE complex assembly. ..
  3. Cabrera M, Ostrowicz C, Mari M, LaGrassa T, Reggiori F, Ungermann C. Vps41 phosphorylation and the Rab Ypt7 control the targeting of the HOPS complex to endosome-vacuole fusion sites. Mol Biol Cell. 2009;20:1937-48 pubmed publisher
    ..Our data suggest that Vps41 phosphorylation fine-tunes the organization of vacuole fusion sites and provide evidence for a fusion "hot spot" on the vacuole limiting membrane. ..
  4. Starai V, Hickey C, Wickner W. HOPS proofreads the trans-SNARE complex for yeast vacuole fusion. Mol Biol Cell. 2008;19:2500-8 pubmed publisher
    ..This is the most direct evidence to date that HOPS is directly involved in the fusion event. ..
  5. Angers C, Merz A. HOPS interacts with Apl5 at the vacuole membrane and is required for consumption of AP-3 transport vesicles. Mol Biol Cell. 2009;20:4563-74 pubmed publisher
    ..We propose that AP-3 remains associated with budded vesicles, interacts with Vps41 and HOPS upon vesicle docking at the vacuole, and finally dissociates during docking or fusion. ..
  6. Brett C, Plemel R, Lobingier B, Lobinger B, Vignali M, Fields S, et al. Efficient termination of vacuolar Rab GTPase signaling requires coordinated action by a GAP and a protein kinase. J Cell Biol. 2008;182:1141-51 pubmed publisher
    ..We further demonstrate that Ypt7 binds not one but two Vps-C/HOPS subunits: Vps39, a putative Ypt7 nucleotide exchange factor, and Vps41...
  7. Price A, Seals D, Wickner W, Ungermann C. The docking stage of yeast vacuole fusion requires the transfer of proteins from a cis-SNARE complex to a Rab/Ypt protein. J Cell Biol. 2000;148:1231-8 pubmed
    ..Thus, cis-SNARE complexes can contain Rab/Ypt effectors, and these effectors can be mobilized by NSF/Sec18p-driven priming, allowing their direct association with a Rab/Ypt protein to activate docking. ..
  8. Peplowska K, Markgraf D, Ostrowicz C, Bange G, Ungermann C. The CORVET tethering complex interacts with the yeast Rab5 homolog Vps21 and is involved in endo-lysosomal biogenesis. Dev Cell. 2007;12:739-50 pubmed
    ..The HOPS complex, in addition, contains Vps41/Vam2 and Vam6, whereas the CORVET complex has the Vps41 homolog Vps8 and the (h)Vam6 homolog Vps3...
  9. Nakamura N, Hirata A, Ohsumi Y, Wada Y. Vam2/Vps41p and Vam6/Vps39p are components of a protein complex on the vacuolar membranes and involved in the vacuolar assembly in the yeast Saccharomyces cerevisiae. J Biol Chem. 1997;272:11344-9 pubmed
    The VAM2/VPS41 and VAM6/VPS39 were shown to encode hydrophilic proteins of 113 and 123 kDa, respectively...
  10. Wurmser A, Sato T, Emr S. New component of the vacuolar class C-Vps complex couples nucleotide exchange on the Ypt7 GTPase to SNARE-dependent docking and fusion. J Cell Biol. 2000;151:551-62 pubmed
    ..Here we demonstrate that the class C-Vps complex contains two additional proteins, Vps39 and Vps41...
  11. Jun Y, Thorngren N, Starai V, Fratti R, Collins K, Wickner W. Reversible, cooperative reactions of yeast vacuole docking. EMBO J. 2006;25:5260-9 pubmed
    ..Docked vacuoles finally assemble SNARE complexes, yet still require physiological temperature and lipid rearrangements to complete fusion. ..
  12. MacDonald C, Piper R. Genetic dissection of early endosomal recycling highlights a TORC1-independent role for Rag GTPases. J Cell Biol. 2017;216:3275-3290 pubmed publisher
    ..subject to metabolic control through the Rag GTPases Gtr1 and Gtr2, which work downstream of the exchange factor Vam6. Gtr1 and Gtr2 control the recycling pathway independently of TORC1 regulation through the Gtr1 interactor Ltv1...
  13. Zurita Martinez S, Puria R, Pan X, Boeke J, Cardenas M. Efficient Tor signaling requires a functional class C Vps protein complex in Saccharomyces cerevisiae. Genetics. 2007;176:2139-50 pubmed
  14. Balderhaar H, Lachmann J, Yavavli E, Bröcker C, Lürick A, Ungermann C. The CORVET complex promotes tethering and fusion of Rab5/Vps21-positive membranes. Proc Natl Acad Sci U S A. 2013;110:3823-8 pubmed publisher
    ..We therefore conclude that CORVET is a tethering complex that promotes fusion of Rab5-positive membranes and thus facilitates receptor down-regulation and recycling at the late endosome. ..
  15. Hoffman Sommer M, Migdalski A, Rytka J, Kucharczyk R. Multiple functions of the vacuolar sorting protein Ccz1p in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2005;329:197-204 pubmed
    ..The mechanisms of Ca(2+)-pump-mediated suppression also differ from each other, since the action of Pmr1p, but not Pmc1p, appears to require Arl1p function. ..
  16. Alpadi K, Kulkarni A, Comte V, Reinhardt M, Schmidt A, Namjoshi S, et al. Sequential analysis of trans-SNARE formation in intracellular membrane fusion. PLoS Biol. 2012;10:e1001243 pubmed publisher
    ..This suggests that the vacuolar Rab-GTPase, Ypt7, and HOPS restrict cis-SNARE disassembly and thereby bias trans-SNARE assembly into a preferred topology. ..
  17. H nscher C, Mari M, Auffarth K, Bohnert M, Griffith J, Geerts W, et al. Cellular metabolism regulates contact sites between vacuoles and mitochondria. Dev Cell. 2014;30:86-94 pubmed publisher
    ..vCLAMPs depend on the vacuolar HOPS tethering complex subunit Vps39/Vam6 and the Rab GTPase Ypt7, which also participate in membrane fusion at the vacuole...
  18. Orr A, Wickner W, Rusin S, Kettenbach A, Zick M. Yeast vacuolar HOPS, regulated by its kinase, exploits affinities for acidic lipids and Rab:GTP for membrane binding and to catalyze tethering and fusion. Mol Biol Cell. 2015;26:305-15 pubmed publisher
    ..After phosphorylation by the vacuolar kinase Yck3p, phospho-HOPS needs both Ypt7p:GTP and acidic lipids to support fusion. ..
  19. Ho R, Stroupe C. The HOPS/Class C Vps Complex Tethers High-Curvature Membranes via a Direct Protein-Membrane Interaction. Traffic. 2016;17:1078-90 pubmed publisher
    ..We propose that HOPS localizes via the Vps41p ALPS motif to these high-curvature regions. There, HOPS binds via Vps39p to Ypt7p in an apposed vacuole membrane. ..
  20. Kulkarni A, Alpadi K, Namjoshi S, Peters C. A tethering complex dimer catalyzes trans-SNARE complex formation in intracellular membrane fusion. Bioarchitecture. 2012;2:59-69 pubmed
    ..Here we report a novel finding that a HOPS tethering complex dimer catalyzes Rab GTPase-dependent formation of a topologically preferred QbQcR-Qa trans-SNARE complex. ..
  21. Parrish W, Stefan C, Emr S. PtdIns(3)P accumulation in triple lipid-phosphatase-deletion mutants triggers lethal hyperactivation of the Rho1p/Pkc1p cell-integrity MAP kinase pathway. J Cell Sci. 2005;118:5589-601 pubmed
    ..Taken together, the results of this study indicated that aberrant Rho1p/Pkc1p signaling contributes to the lethal effects of PtdIns(3)P accumulation in cells deficient in PI 3-phosphatase activity. ..
  22. Chou H, Dukovski D, Chambers M, Reinisch K, Walz T. CATCHR, HOPS and CORVET tethering complexes share a similar architecture. Nat Struct Mol Biol. 2016;23:761-3 pubmed publisher
    ..We also show that HOPS, a tethering complex acting in the endolysosomal pathway, shares a similar architecture, thus suggesting that multisubunit tethering complexes use related structural frameworks. ..
  23. Plemel R, Lobingier B, Brett C, Angers C, Nickerson D, Paulsel A, et al. Subunit organization and Rab interactions of Vps-C protein complexes that control endolysosomal membrane traffic. Mol Biol Cell. 2011;22:1353-63 pubmed publisher
    ..The HOPS-specific subunits, Vps39 and Vps41, also form a subcomplex...
  24. Rana M, Lachmann J, Ungermann C. Identification of a Rab GTPase-activating protein cascade that controls recycling of the Rab5 GTPase Vps21 from the vacuole. Mol Biol Cell. 2015;26:2535-49 pubmed publisher
    ..These data indicate that efficient Vps21 recycling requires both Ypt7 and endosome-vacuole fusion, thus suggesting extended control of a GAP cascade beyond Rab interactions. ..
  25. Brown C, Liu J, Hung G, Carter D, Cui D, Chiang H. The Vid vesicle to vacuole trafficking event requires components of the SNARE membrane fusion machinery. J Biol Chem. 2003;278:25688-99 pubmed
    ..In contrast, the t-SNARE Vam3p was a necessary vacuolar component. Vid vesicle-vacuole trafficking exhibits characteristics similar to heterotypic membrane fusion events. ..
  26. Kingsbury J, Sen N, Maeda T, Heitman J, Cardenas M. Endolysosomal membrane trafficking complexes drive nutrient-dependent TORC1 signaling to control cell growth in Saccharomyces cerevisiae. Genetics. 2014;196:1077-89 pubmed publisher
  27. Behrmann H, Lürick A, Kuhlee A, Balderhaar H, Bröcker C, Kümmel D, et al. Structural identification of the Vps18 β-propeller reveals a critical role in the HOPS complex stability and function. J Biol Chem. 2014;289:33503-12 pubmed publisher
    ..We thus conclude that the β-propeller of Vps18 is required for HOPS stability and function and that it can serve as a starting point for further structural analyses of the HOPS tethering complex. ..