Genomes and Genes
Gene Symbol: SEC4
Description: Rab family GTPase SEC4
Alias: SRO6, Rab family GTPase SEC4
Species: Saccharomyces cerevisiae S288c
- Hicke L, Zanolari B, Pypaert M, Rohrer J, Riezman H. Transport through the yeast endocytic pathway occurs through morphologically distinct compartments and requires an active secretory pathway and Sec18p/N-ethylmaleimide-sensitive fusion protein. Mol Biol Cell. 1997;8:13-31 pubmed
- Adamo J, Moskow J, Gladfelter A, Viterbo D, Lew D, Brennwald P. Yeast Cdc42 functions at a late step in exocytosis, specifically during polarized growth of the emerging bud. J Cell Biol. 2001;155:581-92 pubmed..Rather, we suggest that Cdc42 acts as an allosteric regulator of the vesicle docking and fusion apparatus to provide maximal function at sites of polarized growth. ..
- Pruyne D, Bretscher A. Polarization of cell growth in yeast. J Cell Sci. 2000;113 ( Pt 4):571-85 pubmed..The dynamic arrangement of targeting and recycling provides flexibility for the precise control of morphogenesis. ..
- Wiederkehr A, De Craene J, Ferro Novick S, Novick P. Functional specialization within a vesicle tethering complex: bypass of a subset of exocyst deletion mutants by Sec1p or Sec4p. J Cell Biol. 2004;167:875-87 pubmed..Furthermore, a fraction of Sec1p can be coprecipitated with the exoycst. Our results suggest that Sec1p couples exocyst-mediated vesicle tethering with SNARE-mediated docking and fusion. ..
- Lehman K, Rossi G, Adamo J, Brennwald P. Yeast homologues of tomosyn and lethal giant larvae function in exocytosis and are associated with the plasma membrane SNARE, Sec9. J Cell Biol. 1999;146:125-40 pubmed..Taken together, our studies suggest that members of the lethal giant larvae/tomosyn/Sro7 family play an important role in polarized exocytosis by regulating SNARE function on the plasma membrane. ..
- Grosshans B, Andreeva A, Gangar A, Niessen S, Yates J, Brennwald P, et al. The yeast lgl family member Sro7p is an effector of the secretory Rab GTPase Sec4p. J Cell Biol. 2006;172:55-66 pubmed..b>Sec4-GTP binds to Sro7p in cell extracts as well as to purified Sro7p, and the two proteins can be coimmunoprecipitated...
- Sato Y, Fukai S, Ishitani R, Nureki O. Crystal structure of the Sec4p.Sec2p complex in the nucleotide exchanging intermediate state. Proc Natl Acad Sci U S A. 2007;104:8305-10 pubmed..Unlike the recently reported 3.3 A structure of the Sec4p.Sec2p complex, our structure contains a phosphate ion bound to the P-loop, which may represent an intermediate state of the nucleotide exchange reaction. ..
- 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..Biochemical and genetic experiments demonstrate the importance of these regions, revealing the Vps11 CTD as a key integrator of Vps-C complex assembly, Rab signaling, and endosomal and lysosomal traffic. ..
- Nair J, Muller H, Peterson M, Novick P. Sec2 protein contains a coiled-coil domain essential for vesicular transport and a dispensable carboxy terminal domain. J Cell Biol. 1990;110:1897-909 pubmed..All phenotypes of the temperature-sensitive sec2 alleles are partially suppressed by duplication of the SEC4 gene, but the lethality of a sec2 disruption is not suppressed...
- Collins R, Brennwald P, Garrett M, Lauring A, Novick P. Interactions of nucleotide release factor Dss4p with Sec4p in the post-Golgi secretory pathway of yeast. J Biol Chem. 1997;272:18281-9 pubmedb>SEC4 is an essential gene encoding a small GTPase that is involved in Golgi to cell surface transport in Saccharomyces cerevisiae and is a paradigm for studies on the mode of action of Rab proteins...
- Adamo J, Rossi G, Brennwald P. The Rho GTPase Rho3 has a direct role in exocytosis that is distinct from its role in actin polarity. Mol Biol Cell. 1999;10:4121-33 pubmed..These data suggest that Rho3 acts as a key regulator of cell polarity and exocytosis, coordinating several distinct events for delivery of proteins to specific sites on the cell surface. ..
- Elkind N, Walch Solimena C, Novick P. The role of the COOH terminus of Sec2p in the transport of post-Golgi vesicles. J Cell Biol. 2000;149:95-110 pubmed
- Kozminski K, Alfaro G, Dighe S, Beh C. Homologues of oxysterol-binding proteins affect Cdc42p- and Rho1p-mediated cell polarization in Saccharomyces cerevisiae. Traffic. 2006;7:1224-42 pubmed..Disruption of all OSH gene function caused specific defects in polarized exocytosis, indicating that the Osh proteins are collectively required for a secretory pathway implicated in the maintenance of polarized growth. ..
- Salminen A, Novick P. The Sec15 protein responds to the function of the GTP binding protein, Sec4, to control vesicular traffic in yeast. J Cell Biol. 1989;109:1023-36 pubmed..Duplication of the gene encoding the ras-like, GTP-binding protein, Sec4, can suppress the partial loss of function resulting from the sec15-l mutation, but cannot suppress disruption of ..
- Toikkanen J, Miller K, Söderlund H, Jantti J, Keränen S. The beta subunit of the Sec61p endoplasmic reticulum translocon interacts with the exocyst complex in Saccharomyces cerevisiae. J Biol Chem. 2003;278:20946-53 pubmed..Furthermore, in wild type cells overexpression of SEB1 as well as SEC4 resulted in increased production of secreted proteins...
- Shen D, Yuan H, Hutagalung A, Verma A, Kümmel D, Wu X, et al. The synaptobrevin homologue Snc2p recruits the exocyst to secretory vesicles by binding to Sec6p. J Cell Biol. 2013;202:509-26 pubmed publisher..We propose that the exocyst is recruited to secretory vesicles by the combinatorial signals of Sec4-GTP and the Snc proteins. This could help to confer both specificity and directionality to vesicular traffic.
- Kabcenell A, Goud B, Northup J, Novick P. Binding and hydrolysis of guanine nucleotides by Sec4p, a yeast protein involved in the regulation of vesicular traffic. J Biol Chem. 1990;265:9366-72 pubmedThe 23.5-kDa Sec4 protein is required for vesicular transport between the Golgi apparatus and the plasma membrane in Saccharomyces cerevisiae...
- Govindan B, Bowser R, Novick P. The role of Myo2, a yeast class V myosin, in vesicular transport. J Cell Biol. 1995;128:1055-68 pubmed..Our observations are consistent with a role for Myo2 in transporting a class of secretory vesicles from the mother cell along actin cables into the bud. ..
- Ayscough K, Stryker J, Pokala N, Sanders M, Crews P, Drubin D. High rates of actin filament turnover in budding yeast and roles for actin in establishment and maintenance of cell polarity revealed using the actin inhibitor latrunculin-A. J Cell Biol. 1997;137:399-416 pubmed..Finally, transient actin depolymerization caused many cells to abandon one bud site or mating projection and to initiate growth at a second site. Thus, actin filaments are also required for maintenance of an axis of cell polarity. ..
- Neiman A. Prospore membrane formation defines a developmentally regulated branch of the secretory pathway in yeast. J Cell Biol. 1998;140:29-37 pubmed..The effect of mutations in late-acting genes on sporulation was investigated. Mutation of SEC1, SEC4, or SEC8 blocked spore formation, and electron microscopic analysis of the sec4-8 mutant indicated that this ..
- Imai J, Toh e A, Matsui Y. Genetic analysis of the Saccharomyces cerevisiae RHO3 gene, encoding a rho-type small GTPase, provides evidence for a role in bud formation. Genetics. 1996;142:359-69 pubmed..In addition, we found that SRO6, previously isolated as a multicopy suppressor of rho3, is the same as SEC4...
- Lillie S, Brown S. Smy1p, a kinesin-related protein that does not require microtubules. J Cell Biol. 1998;140:873-83 pubmed..We have also observed a genetic interaction between SMY1 and two of the late SEC mutations, sec2 and sec4. This indicates that Smy1p can play a role even when Myo2p is wild type, and that Smy1p acts at a specific step of ..
- 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. ..
- Zhang X, Wang P, Gangar A, Zhang J, Brennwald P, TerBush D, et al. Lethal giant larvae proteins interact with the exocyst complex and are involved in polarized exocytosis. J Cell Biol. 2005;170:273-83 pubmed..We propose that, although Lgl is broadly distributed in the cells, its localized interaction with the exocyst and kinetic activation are important for the establishment and reenforcement of cell polarity. ..
- Hutagalung A, Coleman J, Pypaert M, Novick P. An internal domain of Exo70p is required for actin-independent localization and mediates assembly of specific exocyst components. Mol Biol Cell. 2009;20:153-63 pubmed publisher..The results suggest that either Exo70p or Sec3p must associate with the plasma membrane for the exocyst to function as a vesicle tether. ..
- Dong G, Medkova M, Novick P, Reinisch K. A catalytic coiled coil: structural insights into the activation of the Rab GTPase Sec4p by Sec2p. Mol Cell. 2007;25:455-62 pubmed..We show that Sec2p is specific for Sec4p and that specificity determinants reside in the two switch regions of Sec4p. ..
- Finger F, Hughes T, Novick P. Sec3p is a spatial landmark for polarized secretion in budding yeast. Cell. 1998;92:559-71 pubmed..We propose that Sec3p is a spatial landmark defining sites of exocytosis. Polarized secretion would result from the coupling of actin-dependent vesicle targeting with Sec3p-dependent establishment of the vesicle fusion site. ..
- Guo W, Roth D, Walch Solimena C, Novick P. The exocyst is an effector for Sec4p, targeting secretory vesicles to sites of exocytosis. EMBO J. 1999;18:1071-80 pubmed..Sec4p may control the assembly of the exocyst. The exocyst may therefore function as a rab effector system for targeted secretion. ..
- Gao X, Albert S, Tcheperegine S, Burd C, Gallwitz D, Bi E. The GAP activity of Msb3p and Msb4p for the Rab GTPase Sec4p is required for efficient exocytosis and actin organization. J Cell Biol. 2003;162:635-46 pubmed..Using a strain defective in polarized secretion and actin-patch organization, we showed that a change in actin-patch organization could be a consequence of the fusion of mistargeted vesicles with the plasma membrane. ..
- Elbert M, Rossi G, Brennwald P. The yeast par-1 homologs kin1 and kin2 show genetic and physical interactions with components of the exocytic machinery. Mol Biol Cell. 2005;16:532-49 pubmed..Genetic analysis suggests that KIN1 and KIN2 act downstream of the Rab-GTPase Sec4, its exchange factor Sec2, and several components of the vesicle tethering complex, the Exocyst...
- Moya M, Roberts D, Novick P. DSS4-1 is a dominant suppressor of sec4-8 that encodes a nucleotide exchange protein that aids Sec4p function. Nature. 1993;361:460-3 pubmed..on members of the ras and rho branches of the superfamily, less is known regarding GDSs that act on members of the Sec4/Ypt1/Rab subgroup...
- Bowser R, Muller H, Govindan B, Novick P. Sec8p and Sec15p are components of a plasma membrane-associated 19.5S particle that may function downstream of Sec4p to control exocytosis. J Cell Biol. 1992;118:1041-56 pubmed..are essential for exocytosis in the yeast Saccharomyces cerevisiae and exhibit strong genetic interactions with SEC4, a gene of the ras superfamily...
- Alfaro G, Johansen J, Dighe S, Duamel G, Kozminski K, Beh C. The sterol-binding protein Kes1/Osh4p is a regulator of polarized exocytosis. Traffic. 2011;12:1521-36 pubmed publisher..These results support a model in which Osh4p acts as a sterol-dependent regulator of polarized vesicle transport, as opposed to being a sterol-transfer protein. ..
- Walch Solimena C, Collins R, Novick P. Sec2p mediates nucleotide exchange on Sec4p and is involved in polarized delivery of post-Golgi vesicles. J Cell Biol. 1997;137:1495-509 pubmed..Sec2p functions as an exchange protein, catalyzing the dissociation of GDP from Sec4 and promoting the binding of GTP...
- 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. ..
- Aalto M, Jantti J, Ostling J, Keranen S, Ronne H. Mso1p: a yeast protein that functions in secretion and interacts physically and genetically with Sec1p. Proc Natl Acad Sci U S A. 1997;94:7331-6 pubmed..Moreover, loss of MSO1 shows synthetic lethality with mutations in SEC1, SEC2, and SEC4, and other synthetic phenotypes with mutations in several other late-acting SEC genes...
- Finger F, Novick P. Sec3p is involved in secretion and morphogenesis in Saccharomyces cerevisiae. Mol Biol Cell. 1997;8:647-62 pubmed..were isolated in a screen for temperature-sensitive secretory mutants that are synthetically lethal with sec4-8. The new sec3 alleles affect early as well as late stages of secretion...
- Santiago Tirado F, Legesse Miller A, Schott D, Bretscher A. PI4P and Rab inputs collaborate in myosin-V-dependent transport of secretory compartments in yeast. Dev Cell. 2011;20:47-59 pubmed publisher..Thus, we show that a coincidence detection mechanism coordinates inputs from PI4P and the appropriate Rab for secretory compartment transport. ..
- Mizuno Yamasaki E, Medkova M, Coleman J, Novick P. Phosphatidylinositol 4-phosphate controls both membrane recruitment and a regulatory switch of the Rab GEF Sec2p. Dev Cell. 2010;18:828-40 pubmed publisher..In this way, the regulation of PI4P levels may switch Sec2p/Sec4p function during vesicle maturation, from a Rab GEF recruitment cascade involving Ypt32p to an effector positive feedback loop involving Sec15p. ..
- Brennwald P, Kearns B, Champion K, Keranen S, Bankaitis V, Novick P. Sec9 is a SNAP-25-like component of a yeast SNARE complex that may be the effector of Sec4 function in exocytosis. Cell. 1994;79:245-58 pubmedTo identify potential Sec4 effectors, we isolated high copy suppressors of a Sec4 effector domain mutant. The most potent of these was found to be SEC9, a gene required for post-Golgi transport...
- Walch Solimena C, Novick P. The yeast phosphatidylinositol-4-OH kinase pik1 regulates secretion at the Golgi. Nat Cell Biol. 1999;1:523-5 pubmed
- Grosshans B, Novick P. Identification and verification of Sro7p as an effector of the Sec4p Rab GTPase. Methods Enzymol. 2008;438:95-108 pubmed publisher..We also describe the methods used to identify and verify one candidate, Sro7p, as a bona fide Sec4p effector. This includes tests of the specificity and efficiency of binding both in vitro and in vivo. ..
- Lepore D, Spassibojko O, Pinto G, Collins R. Cell cycle-dependent phosphorylation of Sec4p controls membrane deposition during cytokinesis. J Cell Biol. 2016;214:691-703 pubmed publisher..Our data suggest the physiological relevance of Sec4p phosphorylation is to facilitate the coordination of membrane-trafficking events during cytokinesis. ..
- Lefebvre F, Prouzet Mauleon V, Hugues M, Crouzet M, Vieillemard A, McCusker D, et al. Secretory pathway-dependent localization of the Saccharomyces cerevisiae Rho GTPase-activating protein Rgd1p at growth sites. Eukaryot Cell. 2012;11:590-600 pubmed publisher..Our data indicate that secretory vesicles are involved in the delivery of RhoGAP Rgd1p to the bud tip and bud neck. ..
- Gilbert P, Burd C. GDP dissociation inhibitor domain II required for Rab GTPase recycling. J Biol Chem. 2001;276:8014-20 pubmed..We conclude that Domain II of Gdi1p is essential for Rab loading and Rab extraction, and confirm that each of these activities is required for Gdi1p function in vivo. ..
- Casavola E, Catucci A, Bielli P, Di Pentima A, Porcu G, Pennestri M, et al. Ypt32p and Mlc1p bind within the vesicle binding region of the class V myosin Myo2p globular tail domain. Mol Microbiol. 2008;67:1051-66 pubmed publisher..Our data are consistent with a role of Ypt32p and Mlc1p in regulating the interaction of post-Golgi carriers with Myo2p subdomain II. ..
- Demmel L, Beck M, Klose C, Schlaitz A, Gloor Y, Hsu P, et al. Nucleocytoplasmic shuttling of the Golgi phosphatidylinositol 4-kinase Pik1 is regulated by 14-3-3 proteins and coordinates Golgi function with cell growth. Mol Biol Cell. 2008;19:1046-61 pubmed publisher..These data suggest a role of Pik1p nucleocytoplasmic shuttling in coordination of biosynthetic transport from the Golgi with nutrient signaling. ..
- Alory C, Balch W. Molecular basis for Rab prenylation. J Cell Biol. 2000;150:89-103 pubmed
- Kim D, Massey T, Sacher M, Pypaert M, Ferro Novick S. Sgf1p, a new component of the Sec34p/Sec35p complex. Traffic. 2001;2:820-30 pubmed..Although an earlier study suggested that Sec34p (Grd20p) is not required for protein secretion, we show here that the sec34-2 and sec35-1 mutations lead to a pleiotropic block in the secretion of all proteins into the growth medium. ..
- Johansen J, Alfaro G, Beh C. Polarized Exocytosis Induces Compensatory Endocytosis by Sec4p-Regulated Cortical Actin Polymerization. PLoS Biol. 2016;14:e1002534 pubmed publisher..Sec4p, or its guanine nucleotide exchange factor (GEF) Sec2p, inhibit actin patch formation, whereas the activating sec4-Q79L mutation accelerates patch assembly...
- Stalder D, Novick P. The casein kinases Yck1p and Yck2p act in the secretory pathway, in part, by regulating the Rab exchange factor Sec2p. Mol Biol Cell. 2016;27:686-701 pubmed publisher..This promotes Sec2p function by stimulating its interaction with Sec15p. Finally, Sec2p is dephosphorylated very late in the exocytic reaction to facilitate recycling. ..
- Watson K, Rossi G, Temple B, Brennwald P. Structural basis for recognition of the Sec4 Rab GTPase by its effector, the Lgl/tomosyn homologue, Sro7. Mol Biol Cell. 2015;26:3289-300 pubmed publisher..The yeast homologue, Sro7, is believed to act as a downstream effector of the Sec4 Rab GTPase to promote soluble N-ethylmaleimide-sensitive factor adaptor protein receptor (SNARE) assembly during ..
- Neller J, DÃ¼nkler A, RÃ¶sler R, Johnsson N. A protein complex containing Epo1p anchors the cortical endoplasmic reticulum to the yeast bud tip. J Cell Biol. 2015;208:71-87 pubmed publisher..This analysis therefore identifies Epo1p as a novel and important component of the polarisome that promotes cER tethering at sites of polarized growth. ..
- Gorynia S, Lorenz T, Costaguta G, Daboussi L, Cascio D, Payne G. Yeast Irc6p is a novel type of conserved clathrin coat accessory factor related to small G proteins. Mol Biol Cell. 2012;23:4416-29 pubmed publisher..Together these results define Irc6p/p34 as a novel type of conserved clathrin accessory protein and founding members of a new G protein-like family. ..
- 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..In our working model, the intrinsic tethering capacity Vps21 operates in concert with conventional effectors and SNAREs to drive efficient docking and fusion. ..
- 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. ..
- Sato Y, Shirakawa R, Horiuchi H, Dohmae N, Fukai S, Nureki O. Asymmetric coiled-coil structure with Guanine nucleotide exchange activity. Structure. 2007;15:245-52 pubmed..The present functional analyses allow us to build the Sec2p:Sec4p complex model, which explains the specificity for Rab GTPases by their respective GEF proteins. ..
- Singh J, Tyers M. A Rab escort protein integrates the secretion system with TOR signaling and ribosome biogenesis. Genes Dev. 2009;23:1944-58 pubmed publisher..The Sfp1-Mrs6 interaction is a nexus for growth regulation that links the secretory system and TOR-dependent nutrient signaling to ribosome biogenesis. ..
- Dighe S, Kozminski K. Secretory vesicles deliver Cdc42p to sites of polarized growth in S. cerevisiae. PLoS ONE. 2014;9:e99494 pubmed publisher..Here we show with S. cerevisiae that Cdc42p associates with secretory vesicles in vivo. ..
- Geng J, Nair U, Yasumura Yorimitsu K, Klionsky D. Post-Golgi Sec proteins are required for autophagy in Saccharomyces cerevisiae. Mol Biol Cell. 2010;21:2257-69 pubmed publisher..Here, we report that two post-Golgi proteins, Sec2 and Sec4, are required for autophagy. Sec4 is a Rab family GTPase, and Sec2 is its guanine nucleotide exchange factor...