title: New component of the vacuolar class C-Vps complex couples nucleotide exchange on the Ypt7 GTPase to SNARE-dependent docking and fusion.
abstract: The class C subset of vacuolar protein sorting (Vps) proteins (Vps11, Vps18, Vps16 and Vps33) assembles into a vacuole/prevacuole-associated complex. Here we demonstrate that the class C-Vps complex contains two additional proteins, Vps39 and Vps41. The COOH-terminal 148 amino acids of Vps39 direct its association with the class C-Vps complex by binding to Vps11. A previous study has shown that a large protein complex containing Vps39 and Vps41 functions as a downstream effector of the active, GTP-bound form of Ypt7, a rab GTPase required for the fusion of vesicular intermediates with the vacuole (Price, A., D. Seals, W. Wickner, and C. Ungermann. 2000. J. Cell Biol. 148:1231-1238). Here we present data that indicate that this complex also functions to stimulate nucleotide exchange on Ypt7. We show that Vps39 directly binds the GDP-bound and nucleotide-free forms of Ypt7 and that purified Vps39 stimulates nucleotide exchange on Ypt7. We propose that the class C-Vps complex both promotes Vps39-dependent nucleotide exchange on Ypt7 and, based on the work of Price et al., acts as a Ypt7 effector that tethers transport vesicles to the vacuole. Thus, the class C-Vps complex directs multiple reactions during the docking and fusion of vesicles with the vacuole, each of which contributes to the overall specificity and efficiency of this transport process.
authors.affiliation: Division of Cellular and Molecular Medicine and Howard Hughes Medical Institute, University of California at San Diego, School of Medicine, La Jolla, California 92093, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Wurmser
authors.forename: T K
authors.initials: TK
authors.lastname: Sato
authors.forename: S D
authors.initials: SD
authors.lastname: Emr
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D017124:Conserved Sequence; D005656:Fungal Proteins / Q000378:metabolism; D020043:Genes, Essential / Q000235:genetics; D006160:Guanosine Triphosphate / Q000378:metabolism*; D046911:Macromolecular Substances; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000378:metabolism; D050600:SNARE Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques; D014617:Vacuoles / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; C077734:NPL3 protein, S cerevisiae; D009687:Nuclear Proteins; C065710:PEP5 protein, S cerevisiae; D016601:RNA-Binding Proteins; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; C406817:VAM6 protein, S cerevisiae; C083878:VPS41 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D006160:Guanosine Triphosphate; C079005:YPT7 protein, S cerevisiae; D020691:rab GTP-Binding Proteins