VPS21

Summary

Gene Symbol: VPS21
Description: Rab family GTPase VPS21
Alias: VPS12, VPT12, YPT21, YPT51, Rab family GTPase VPS21
Species: Saccharomyces cerevisiae S288c
Products:     VPS21

Top Publications

  1. Hama H, Tall G, Horazdovsky B. Vps9p is a guanine nucleotide exchange factor involved in vesicle-mediated vacuolar protein transport. J Biol Chem. 1999;274:15284-91 pubmed
    ..The gene affected in one of these mutants, VPS21, encodes a member of the Sec4/Ypt/Rab family of small GTPases...
  2. Pawelec A, Arsić J, Kölling R. Mapping of Vps21 and HOPS binding sites in Vps8 and effect of binding site mutants on endocytic trafficking. Eukaryot Cell. 2010;9:602-10 pubmed publisher
    ..of the class C/HOPS core complex and, contrary to a previous report, also independent of the Rab GTPase Vps21. Our data indicate that Vps8 makes multiple contacts with membranes...
  3. 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
    ..subunits, Vps3 and Vps8, form a subcomplex and physically and genetically interact with the Rab5 orthologue Vps21. The HOPS-specific subunits, Vps39 and Vps41, also form a subcomplex...
  4. Lachmann J, Barr F, Ungermann C. The Msb3/Gyp3 GAP controls the activity of the Rab GTPases Vps21 and Ypt7 at endosomes and vacuoles. Mol Biol Cell. 2012;23:2516-26 pubmed publisher
    ..In yeast, the Rab5 GTPase Vps21 controls fusion and membrane dynamics between early and late endosomes...
  5. Raymond C, Howald Stevenson I, Vater C, Stevens T. Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants. Mol Biol Cell. 1992;3:1389-402 pubmed
    ..A good correlation between morphological phenotype and the extent of the CPY sorting defect was observed. ..
  6. Horazdovsky B, Cowles C, Mustol P, Holmes M, Emr S. A novel RING finger protein, Vps8p, functionally interacts with the small GTPase, Vps21p, to facilitate soluble vacuolar protein localization. J Biol Chem. 1996;271:33607-15 pubmed
    ..In vps21 null mutant cells, Vps8p is found in the cytosol...
  7. Du L, Collins R, Novick P. Identification of a Sec4p GTPase-activating protein (GAP) as a novel member of a Rab GAP family. J Biol Chem. 1998;273:3253-6 pubmed
    ..The finding that yeast Rab GAPs share homology with proteins in other species, such as Caenorhabditis elegans and human, suggests the existence of a conserved Rab GAP family. ..
  8. Albert S, Gallwitz D. Msb4p, a protein involved in Cdc42p-dependent organization of the actin cytoskeleton, is a Ypt/Rab-specific GAP. Biol Chem. 2000;381:453-6 pubmed
    ..Purified Msb4p/Gyp4p acts primarily on Sec4p, Ypt6p and Ypt7p and might have a role in polarized secretion. ..
  9. Cabrera M, Arlt H, Epp N, Lachmann J, Griffith J, Perz A, et al. Functional separation of endosomal fusion factors and the class C core vacuole/endosome tethering (CORVET) complex in endosome biogenesis. J Biol Chem. 2013;288:5166-75 pubmed publisher
    ..Moreover, when we compared the ultrastructure, CORVET mutants were most similar to deletions of the Rab Vps21 and its guanine nucleotide exchange factor Vps9 and different from vac1 deletion, indicating separate functions...

More Information

Publications51

  1. 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 propose that signal propagation through the Ypt7 pathway is controlled by integrated feedback and feed-forward loops. In this model, Yck3 enforces a requirement for the activated Rab in docking and fusion. ..
  2. Luan P, Balch W, Emr S, Burd C. Molecular dissection of guanine nucleotide dissociation inhibitor function in vivo. Rab-independent binding to membranes and role of Rab recycling factors. J Biol Chem. 1999;274:14806-17 pubmed
  3. Nickerson D, Russell M, Lo S, Chapin H, Milnes J, Merz A. Termination of isoform-selective Vps21/Rab5 signaling at endolysosomal organelles by Msb3/Gyp3. Traffic. 2012;13:1411-1428 pubmed publisher
    ..Like humans, Saccharomyces cerevisiae has three Rab5s (Vps21, Ypt52 and Ypt53) and one Rab7 (Ypt7). Here, we elucidate the functional roles and regulation of the yeast Rab5s...
  4. Markgraf D, Ahnert F, Arlt H, Mari M, Peplowska K, Epp N, et al. The CORVET subunit Vps8 cooperates with the Rab5 homolog Vps21 to induce clustering of late endosomal compartments. Mol Biol Cell. 2009;20:5276-89 pubmed publisher
    ..In particular, our results indicate that Vps8 interacts and cooperates with the activated Rab5 homolog Vps21 to induce the clustering of late endosomal membranes, indicating that Vps8 is the effector subunit of the CORVET ..
  5. Tall G, Hama H, DeWald D, Horazdovsky B. The phosphatidylinositol 3-phosphate binding protein Vac1p interacts with a Rab GTPase and a Sec1p homologue to facilitate vesicle-mediated vacuolar protein sorting. Mol Biol Cell. 1999;10:1873-89 pubmed
    ..We have constructed an activated allele of VPS21, a yeast Rab protein involved in vacuolar protein sorting, and demonstrated an allele-specific interaction between ..
  6. Singer Krüger B, Stenmark H, Düsterhöft A, Philippsen P, Yoo J, Gallwitz D, et al. Role of three rab5-like GTPases, Ypt51p, Ypt52p, and Ypt53p, in the endocytic and vacuolar protein sorting pathways of yeast. J Cell Biol. 1994;125:283-98 pubmed
    ..identify rab5 homologs in Saccharomyces cerevisiae, two genes encoding proteins with 54 and 52% identity to rab5, YPT51 and YPT53 have been identified...
  7. Kucharczyk R, Hoffman Sommer M, Piekarska I, von Mollard G, Rytka J. The Saccharomyces cerevisiae protein Ccz1p interacts with components of the endosomal fusion machinery. FEMS Yeast Res. 2009;9:565-73 pubmed publisher
    ..ccz1Delta mutation with deletions of PEP12 or other genes encoding components of the endosomal fusion machinery, VPS21, VPS9 or VPS45, results in synthetic growth phenotypes...
  8. Peterson M, Emr S. The class C Vps complex functions at multiple stages of the vacuolar transport pathway. Traffic. 2001;2:476-86 pubmed
    ..Collectively, these results indicate that the Class C Vps complex plays essential roles in the processes of membrane docking and fusion at both the Golgi-to-endosome and endosome-to-vacuole stages of transport. ..
  9. 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
    ..HOPS complex at the vacuole and a novel endosomal tethering (CORVET) complex, which interacts with the Rab GTPase Vps21. Both complexes share the four class C Vps proteins: Vps11, Vps16, Vps18, and Vps33...
  10. Albert S, Gallwitz D. Two new members of a family of Ypt/Rab GTPase activating proteins. Promiscuity of substrate recognition. J Biol Chem. 1999;274:33186-9 pubmed
    ..The results demonstrate that in yeast there is a large family of Ypt/Rab-GAPs, members of which discriminate poorly between GTPases involved in regulating different steps of exo- and endocytic transport routes. ..
  11. Peterson M, Burd C, Emr S. Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome. Curr Biol. 1999;9:159-62 pubmed
  12. Epp N, Ungermann C. The N-terminal domains of Vps3 and Vps8 are critical for localization and function of the CORVET tethering complex on endosomes. PLoS ONE. 2013;8:e67307 pubmed publisher
    ..For fusion, the heterohexameric CORVET complex as an effector of the endosomal Rab5/Vps21 GTPase has a central function in the initial tethering event...
  13. Liu T, Gomez T, Sackey B, Billadeau D, Burd C. Rab GTPase regulation of retromer-mediated cargo export during endosome maturation. Mol Biol Cell. 2012;23:2505-15 pubmed publisher
    ..Thus retromer has dual roles in retrograde cargo export and in controlling the fusion dynamics of the late endovacuolar system. ..
  14. Bensen E, Costaguta G, Payne G. Synthetic genetic interactions with temperature-sensitive clathrin in Saccharomyces cerevisiae. Roles for synaptojanin-like Inp53p and dynamin-related Vps1p in clathrin-dependent protein sorting at the trans-Golgi network. Genetics. 2000;154:83-97 pubmed
    ..Our findings implicate a wide variety of proteins in clathrin-dependent processes and provide evidence for the selective involvement of Inp53p in clathrin-mediated protein sorting at the TGN. ..
  15. Gilbert P, Burd C. GDP dissociation inhibitor domain II required for Rab GTPase recycling. J Biol Chem. 2001;276:8014-20 pubmed
    ..In a second gdi1 mutant, the endosomal/vacuolar Rabs Vps21/Ypt51p and Ypt7p accumulated in the cytosol bound to Gdi1p, but localization of Ypt1p and Sec4p were not ..
  16. Stepp J, Huang K, Lemmon S. The yeast adaptor protein complex, AP-3, is essential for the efficient delivery of alkaline phosphatase by the alternate pathway to the vacuole. J Cell Biol. 1997;139:1761-74 pubmed
    ..We suggest that some AP-3-dependent cargo proteins that regulate late steps in Golgi to vacuole transport are diverted into the Vps pathway allowing completion of transfer to the vacuole in the class E vps mutant. ..
  17. Chen C, Calero M, DeRegis C, Heidtman M, Barlowe C, Collins R. Genetic analysis of yeast Yip1p function reveals a requirement for Golgi-localized rab proteins and rab-Guanine nucleotide dissociation inhibitor. Genetics. 2004;168:1827-41 pubmed
  18. Prescianotto Baschong C, Riezman H. Ordering of compartments in the yeast endocytic pathway. Traffic. 2002;3:37-49 pubmed
    ..On the other hand, traffic to the early recycling endosome is less dependent on Rab5 homologs and does not require Vps27p. ..
  19. Lo S, Brett C, Plemel R, Vignali M, Fields S, Gonen T, et al. Intrinsic tethering activity of endosomal Rab proteins. Nat Struct Mol Biol. 2011;19:40-7 pubmed publisher
    ..Using chemically defined reaction systems, we discovered that Vps21, a Saccharomyces cerevisiae ortholog of mammalian endosomal Rab5, functions in trans with itself and with at least ..
  20. Esters H, Alexandrov K, Constantinescu A, Goody R, Scheidig A. High-resolution crystal structure of S. cerevisiae Ypt51(DeltaC15)-GppNHp, a small GTP-binding protein involved in regulation of endocytosis. J Mol Biol. 2000;298:111-21 pubmed
    ..We present the 1.5 A high-resolution crystal structure of Ypt51 in its active, GppNHp-bound conformation...
  21. Calero M, Chen C, Zhu W, Winand N, Havas K, Gilbert P, et al. Dual prenylation is required for Rab protein localization and function. Mol Biol Cell. 2003;14:1852-67 pubmed
  22. Lipatova Z, Segev N. A Role for Macro-ER-Phagy in ER Quality Control. PLoS Genet. 2015;11:e1005390 pubmed publisher
    ..three sequential steps of this pathway are delineated: Atg9-dependent exit from the ER en route to autophagy, Ypt1- and core Atgs-mediated pre-autophagsomal-structure organization, and Ypt51-mediated delivery of APs to the vacuole.
  23. Zabrocki P, Bastiaens I, Delay C, Bammens T, Ghillebert R, Pellens K, et al. Phosphorylation, lipid raft interaction and traffic of alpha-synuclein in a yeast model for Parkinson. Biochim Biophys Acta. 2008;1783:1767-80 pubmed publisher
  24. Jensen L, Carroll M, Hall M, Harvey C, Beese S, Culotta V. Down-regulation of a manganese transporter in the face of metal toxicity. Mol Biol Cell. 2009;20:2810-9 pubmed publisher
    ..We provide evidence that manganese starvation is sensed within the lumen of the secretory pathway, whereas manganese toxicity is sensed within an extra-Golgi/cytosolic compartment of the cell. ..
  25. John Peter A, Lachmann J, Rana M, Bunge M, Cabrera M, Ungermann C. The BLOC-1 complex promotes endosomal maturation by recruiting the Rab5 GTPase-activating protein Msb3. J Cell Biol. 2013;201:97-111 pubmed publisher
    ..The yeast BLOC-1 consisted of six subunits, which localized interdependently to the endosomes in a Rab5/Vps21-dependent manner...
  26. 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
    ..We previously identified the hexameric BLOC-1 complex as an effector of the yeast Rab5 Vps21, which also recruits the GTPase-activating protein (GAP) Msb3...
  27. 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
    ..analogies with the HOPS complex, we set up an in vitro system, and establish CORVET as a bona-fide tether for Vps21-positive endosome/vacuole membranes. Purified CORVET binds to SNAREs and Rab5/Vps21-GTP...
  28. Toshima J, Nishinoaki S, Sato Y, Yamamoto W, Furukawa D, Siekhaus D, et al. Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole. Nat Commun. 2014;5:3498 pubmed publisher
    ..We propose that the endocytic traffic branches into two routes to reach the vacuole: a Rab5-dependent VPS pathway and a Rab5-independent AP-3-mediated pathway. ..
  29. Liu Y, Nakatsukasa K, Kotera M, Kanada A, Nishimura T, Kishi T, et al. Non-SCF-type F-box protein Roy1/Ymr258c interacts with a Rab5-like GTPase Ypt52 and inhibits Ypt52 function. Mol Biol Cell. 2011;22:1575-84 pubmed publisher
    ..The Rab5-like small guanosine 5'-triphosphatase Vps21/Ypt51 is a key regulator of intracellular transportation; however, deletion of its isoforms, Ypt52 and Ypt53, ..
  30. Germann M, Swain E, Bergman L, Nickels J. Characterizing the sphingolipid signaling pathway that remediates defects associated with loss of the yeast amphiphysin-like orthologs, Rvs161p and Rvs167p. J Biol Chem. 2005;280:4270-8 pubmed
    ..Based on our results, we suggest that sphingolipid-dependent suppression of rvs defects may not work entirely through regulating changes in actin organization. ..
  31. Calero M, Winand N, Collins R. Identification of the novel proteins Yip4p and Yip5p as Rab GTPase interacting factors. FEBS Lett. 2002;515:89-98 pubmed
  32. Zanolari B, Rockenbauch U, Trautwein M, Clay L, Barral Y, Spang A. Transport to the plasma membrane is regulated differently early and late in the cell cycle in Saccharomyces cerevisiae. J Cell Sci. 2011;124:1055-66 pubmed publisher
    ..We propose that transport to and from the bud neck is regulated differently in small- and large-budded cells, and differs early and late in the cell cycle. ..
  33. Conibear E, Stevens T. Vps52p, Vps53p, and Vps54p form a novel multisubunit complex required for protein sorting at the yeast late Golgi. Mol Biol Cell. 2000;11:305-23 pubmed
    ..The Vps52/53/54 complex joins a growing list of distinct multisubunit complexes that regulate membrane-trafficking events. ..
  34. Will E, Albert S, Gallwitz D. Expression, purification, and biochemical properties of Ypt/Rab GTPase-activating proteins of Gyp family. Methods Enzymol. 2001;329:50-8 pubmed
  35. Singer Krüger B, Ferro Novick S. Use of a synthetic lethal screen to identify yeast mutants impaired in endocytosis, vacuolar protein sorting and the organization of the cytoskeleton. Eur J Cell Biol. 1997;74:365-75 pubmed
    ..and vacuolar protein sorting pathways, we screened for mutants that display synthetic growth defects with delta ypt51, a mutant impaired in membrane traffic at a point where these pathways intersect...
  36. Russell M, Shideler T, Nickerson D, West M, Odorizzi G. Class E compartments form in response to ESCRT dysfunction in yeast due to hyperactivity of the Vps21 Rab GTPase. J Cell Sci. 2012;125:5208-20 pubmed publisher
    ..We found class E compartment formation requires Vps21, which is orthologous to the Rab5A GTPase in metazoans that promotes fusion of endocytic vesicles with early ..
  37. Bridges D, Fisher K, Zolov S, Xiong T, Inoki K, Weisman L, et al. Rab5 proteins regulate activation and localization of target of rapamycin complex 1. J Biol Chem. 2012;287:20913-21 pubmed publisher
    ..disrupt mTORC1 activation and localization in mammalian cells, whereas disruption of the Rab5 homolog in yeast, Vps21, leads to decreased TORC1 function...
  38. Zhao X, Chang A, Toh e A, Arvan P. A role for Lte1p (a low temperature essential protein involved in mitosis) in proprotein processing in the yeast secretory pathway. J Biol Chem. 2007;282:1670-8 pubmed
    ..By contrast, a vps21 mutant produces a synthetic defect with lte1 in proprotein processing, as well as a synthetic growth defect...
  39. Chen C, Collins R. Insights into biological functions across species: examining the role of Rab proteins in YIP1 family function. Biochem Soc Trans. 2005;33:614-8 pubmed
    ..e. independent or dependent activities of Yip1p. ..
  40. Calero M, Collins R. Saccharomyces cerevisiae Pra1p/Yip3p interacts with Yip1p and Rab proteins. Biochem Biophys Res Commun. 2002;290:676-81 pubmed
    ..The interactions between Pra1p/Yip3p and Rab proteins are dependent on the presence of the Rab protein C-terminal cysteines and require C-terminal prenylation. ..
  41. Nakatsukasa K, Kanada A, Matsuzaki M, Byrne S, Okumura F, Kamura T. The nutrient stress-induced small GTPase Rab5 contributes to the activation of vesicle trafficking and vacuolar activity. J Biol Chem. 2014;289:20970-8 pubmed
    ..Under non-stress conditions, Vps21, a constitutively expressed Rab5 isoform, is crucial to Golgi-vacuole trafficking and to vacuolar hydrolase ..
  42. Paulsel A, Merz A, Nickerson D. Vps9 family protein Muk1 is the second Rab5 guanosine nucleotide exchange factor in budding yeast. J Biol Chem. 2013;288:18162-71 pubmed publisher
    ..have trafficking defects considerably less severe than multiple deletions of the three cognate Rab5 paralogs (Vps21, Ypt52, and Ypt53)...