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Small GTPases and Vesicle Trafficking: Sec4p and its Interaction with Up- and Downstream Elements

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GTPases in Biology I

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 108 / 1))

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Abstract

Eukaryotic cells are characterized by the presence of many intracellular membrane bounded organelles. Transfer of material from one organelle to another is generally mediated by vesicular transport. By this mechanism, a vesicle buds from a donor organelle and migrates through the cytoplasm until it recognizes the appropriate target organelle (Palade 1975; for a recent review see Rothman and Orci 1992). The fusion of the vesicle membrane with that of the target organelle completes the transfer of both membrane constituents and lumenal contents. The wide variety of potential donors and potential targets necessitates an efficient mechanism for maintaining the specificity of the transport process. This can be separated into two distinct steps. First, the appropriate proteins must be incorporated into a transport vesicle. This process is known as sorting and involves a collection of membrane-bound receptors and cytoplasmically disposed coat proteins that serve to define the vesicle constituents. The second, and equally important step, is the process by which each vesicle is brought into contact with the appropriate target organelle. While cytoskeletal elements are involved in the transport of vesicles to the appropriate region of the cell, a membrane-membrane recognition mechanism also must be involved since different target organelles can exist in very close proximity. Over the last 5 years, much attention has been focused on a particular class of ras-related GTP binding proteins as possible elements of the molecular machinery that generates the high degree of specificity required for this vesicle-target recognition process.

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References

  • Adari H, Lowy DR, Willumsen BM, Der CJ, McCormick F (1988) Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain. Science 240:518–521

    Article  PubMed  CAS  Google Scholar 

  • Araki S, Kikuchi A, Hata Y, Isomura M, Takai Y (1990) Regulation of reversible binding of smg p25A, a ras p21-like GTP-binding protein, to synaptic plasma membranes and vesicles by its specific regulatory protein, GDP dissociation inhibitor. J Biol Chem 265:13007–13015

    PubMed  CAS  Google Scholar 

  • Bacon RA, Salminen A, Ruohola HNP, Ferro-Novick S (1989) The GTP-binding protein Ypt1 is required for transport in vitro: The golgi apparatus is defective in yptl mutants. J Cell Biol 109:1015–1022

    Article  PubMed  CAS  Google Scholar 

  • Baker D, Wuestehube L, Schekman R, Botstein D, Segev N (1990) GTP-binding Yptl protein and Ca2+ function independently in a cell-free protein transport reaction. Proc Natl Acad Sci USA 87:355–359

    Article  PubMed  CAS  Google Scholar 

  • Barbacid M (1987) ras Genes. Annu Rev Biochem 56:779–827

    Article  PubMed  CAS  Google Scholar 

  • Becker J, Tan TJ, Trepte HH, Galwitz D (1991) Mutational analysis of the putative effector domain of the GTP-binding Yptl protein suggests specific regulation by a novel GAP activity. EMBO J 10:785–792

    PubMed  CAS  Google Scholar 

  • Bourne HR (1988) Do GTPases direct membrane traffic in secretion? Cell 53:669–671

    Article  PubMed  CAS  Google Scholar 

  • Bourne HR, Sanders DA, McCormick F (1990) The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348:125–132

    Article  PubMed  CAS  Google Scholar 

  • Bowser R, Novick P (1991) Secl5 protein, an essential component of the exocytic apparatus, is associated with the plasma membrane and with a soluble 19.5S particle. J Cell Biol 112:1117–1131

    Article  PubMed  CAS  Google Scholar 

  • Bowser R, Muller H, Govindan B, Novick P (1992) Sec8p and Secl5p are components of a plasma membrane associated 19.5S particle that may function downstream of Sec4p to control exocytosis. J Cell Biol 118:1041–1056

    Article  PubMed  CAS  Google Scholar 

  • Burstein ES, Macara IG (1992) Characterization of a guanine nucleotide releasing factor and a GTPase-activating protein that are specific for the ras-related protein p25 rab3A. Proc Natl Acad Sci USA 89:1154–1158

    Article  PubMed  CAS  Google Scholar 

  • Burstein ES, Linko-Stenz K, Macara IG (1991) Regulation of the GTPase activity of the ras-like protein p25rab3A: evidence for a rab3A specific GAP. J Biol Chem 266:2689–2692

    PubMed  CAS  Google Scholar 

  • Burton J, Roberts D, Montaldi M, Novick P, De Camilli P (1993) A mammalian guanine-nucleotide-releasing protein enhances function of yeast secretory protein Sec4. Nature 361:464–467

    Article  PubMed  CAS  Google Scholar 

  • Chavrier P, Parton RG, Hauri HP, Simons K, Zerial M (1990a) Localization of low molecular weight GTP-binding proteins to exocytic and endocytic compartments. Cell 62:317–329

    Article  PubMed  CAS  Google Scholar 

  • Chavrier P, Vingron M, Sander C, Simons K, Zerial M (1990b) Molecular cloning of YPT1/SEC4-related cDNAs from an epithelial cell line. Mol Cell Biol 10: 6578–6585

    PubMed  CAS  Google Scholar 

  • Chavrier P, Simons K, Zerial M (1992) The complexity of the Rab and Rho GTP-binding protein subfamilies revealed by a PCR cloning approach. Gene 112: 261–264

    Article  PubMed  CAS  Google Scholar 

  • Darchen F, Zahraoui A, Hammel F, Monteils M, Tavitian A, Scherman D (1990) Association of the GTP-binding protein rab3A with bovine adrenal chromaffin granules. Proc Natl Acad Sci USA 87:5692–5696

    Article  PubMed  CAS  Google Scholar 

  • Downward J, Riel R, Wu L, Weinberg R (1990) Identification of a nucleotide exchange promoting activity for p21 ras. Proc Natl Acad Sci USA 87:5998–6002

    Article  PubMed  CAS  Google Scholar 

  • Elferink LA, Anzai K, Scheller RH (1992) rab15, a novel low molecular weight GTP-binding protein specifically expressed in rat brain. J Biol Chem 267: 5768–5775

    PubMed  CAS  Google Scholar 

  • Field J, Nikawa J, Broek D, MacDonald B, Rodgers L, Wilson I, Lerner R, Wigler M (1988) Purification of a RAS-responsive adenyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method. Mol Cell Biol 8:2159–2165

    PubMed  CAS  Google Scholar 

  • Fischer von Mollard G, Mignery GA, Baumert M, Perin MS, Hanson TJ, Burger PM, Jahn R, Sudhof TC (1990) rab3 is a small GTP-binding protein exclusively localized to synaptic vesicles. Proc Natl Acad Sci USA 87:1988–1992

    Article  Google Scholar 

  • Garrett MD, Self AJ, van Oers C, Hall A (1989) Identification of distinct cytoplasmic targets for ras/Rras and rho regulatory proteins. J Biol Chem 264:10–13

    PubMed  CAS  Google Scholar 

  • Gibbs JB, Schaber MD, Allard WJ, Sigal IS, Scolnick EM (1988) Purification of ras GTPase activating protein from bovine brain. Proc Natl Acad Sci USA 85:5026–5030

    Article  PubMed  CAS  Google Scholar 

  • Gorvel JP, Chavrier P, Zerial M, Gruenberg J (1991) Rab5 controls early endosome fusion in vitro. Cell 64:915–925

    Article  PubMed  CAS  Google Scholar 

  • Goud B, Salminen A, Walworth N, Novick PJ (1988) A GTP-binding protein required for secretion rapid associates with secretory vesicles and the plasma membrane in yeast. Cell 53:753–768

    Article  PubMed  CAS  Google Scholar 

  • Goud B, Zahraoui A, Tavitian A, Saraste J (1990) A small GTP-binding protein associated with the Golgi. Nature 345:553–556

    Article  PubMed  CAS  Google Scholar 

  • Haubruck H, Disela C, Wagner P, Gallwitz D (1987) The ras-related ypt protein is an ubiquitous eukaryotic protein: isolation and sequence analysis of mouse cDNA clones highly homologous to the yeast YPT1 gene. EMBO J 6:4049–4053

    PubMed  CAS  Google Scholar 

  • Huang Y, Kung H, Kamata T (1990) Purification of a factor capable of stimulating the guanine nucleotide exchange reaction of ras proteins and its effect on ras small molecular mass G proteins. Proc Natl Acad Sci USA 87:8008–8012

    Article  PubMed  CAS  Google Scholar 

  • Isomura M, Kikuchi A, Ohga N, Takai Y (1991) Regulation of binding of rhoB p20 to membranes by its specific regulatory protein, GDP dissociation inhibitor. Oncogene 6:119–124

    PubMed  CAS  Google Scholar 

  • Jena BP, Brennwald P, Garrett M, Novick P, Jamieson JD (1992) Distinct GAP’s in mammalian pancreas act on the yeast GTP-binding proteins Ypt1 and Sec4. FEBS Lett 309:5–9

    Article  PubMed  CAS  Google Scholar 

  • Kabcenell AK, Goud B, Northup JK, Novick PJ (1990) Binding and hydrolysis of guanine nucleotides by Sec4p, a yeast protein involved in the regulation of vesicular traffic. J Biol Chem 265:9366–9372

    PubMed  CAS  Google Scholar 

  • Kaibuchi K, Mizuno T, Fujioka H, Yamamoto T, Kishi K, Fukumoto Y, Hori Y, Takai Y (1991) Molecular cloning of the cDNA for stimulatory GDP/GTP exchange protein for smg p21s (ras p21-like small GTP-binding proteins) and characterization of stimulatory GDP/GTP exchange protein. Mol Cell Biol 11:2873–2880

    PubMed  CAS  Google Scholar 

  • Kaziro Y (1978) The role of guanosine 5′-triphosphate in polypeptide chain elongation. Biochem Biophys Acta 505:95–127

    PubMed  CAS  Google Scholar 

  • Krengel U, Schlichting I, Scherer A, Schuhman R, Frech M, John J, Kabsch W, Pai E, Wittinghofer A (1990) Three-dimensional structure of H-ras mutants: molecular basis for their inability to function as signal switch molecules. Cell 62:609–617

    Article  Google Scholar 

  • Matsui Y, Kikuchi A, Kondo J, Hishida T, Teranishi Y, Takai Y (1988) Nucleotide and deduced amino acid sequence of GTP-binding protein family with molecular weight of 25000 from bovine brain. J Biol Chem 263:11071–11074

    PubMed  CAS  Google Scholar 

  • Matsui Y, Kikuchi A, Araki S, Hata Y, Kondo J, Teranishi Y, Takai Y (1990) Molecular cloning and characterization of a novel type of regulatory protein (GDI) for smg p25A, a ras-like GTP-binding protein. Mol Cell Biol 10:4116–4122

    PubMed  CAS  Google Scholar 

  • Milburn MV, Tong L, deVos AM, Brunger A, Yamaizumi Z, Nishimura S, Kim SH (1990) Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins. Science 247:939–945

    Article  PubMed  CAS  Google Scholar 

  • Mizoguchi A, Kim S, Ueda T, Kikuchi A, Yorifuji H, Hirokawa N, Takai Y (1990) Localization and subcellular distribution of smg p25A, a ras p21-like GTP-binding protein, in rat brain. J Biol Chem 265:11872–11879

    PubMed  CAS  Google Scholar 

  • Moya M, Roberts D, Novick P (1993) DSS4-1, is a dominant suppressor or sec4-8 that encodes a nucleotide exchange protein that aids Sec4p function. Nature 361:460–463

    Article  PubMed  CAS  Google Scholar 

  • Novick P, Field C, Schekman R (1980) Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 21: 205–215

    Article  PubMed  CAS  Google Scholar 

  • Novick PJ, Goud B, Salminen A, Walworth NC, Nair J, Potenza M (1988) Regulation of vesicular traffic by a GTP-binding protein on the cytoplasmic surface of secretory vesicles in yeast. Cold Spring Harbor Symp Quant. Biol 53:637–647

    CAS  Google Scholar 

  • Padfield PJ, Balch WE, Jamieson JD (1992) A synthetic peptide of the rab3a effector domain stimulates amylase release from permeabilized pancreatic acini. Proc Natl Acad Sci USA 89:1656–1660

    Article  PubMed  CAS  Google Scholar 

  • Pai EF, Kabash W, Krengel U, Holmes KC, John J, Wittinghofer A (1989) Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature 341:209–214

    Article  PubMed  CAS  Google Scholar 

  • Palade G (1975) Intracellular aspects of the process of protein secretion. Science 189:347–358

    Article  PubMed  CAS  Google Scholar 

  • Plutner H, Schwaninger R, Pind S, Balch WE (1990) Synthetic peptides of the Rab effector domain inhibit vesicular transport through the secretory pathway. EMBO J 9:2375–2383

    PubMed  CAS  Google Scholar 

  • Plutner H, Cox A, Pind S, Khosravi-Far R, Bourne J, Swaninger R, Der C, Balch W (1991) Rab1 regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments. J Cell Biol 115:31–43

    Article  PubMed  CAS  Google Scholar 

  • Robinson L, Gibbs J, Marshall M, Sigal I, Tatchell K (1987) CDC25: a component of the RAS-adenylate cyclase pathway in Saccharomyces cerevisiae. Science 235:1218–1221

    Article  PubMed  CAS  Google Scholar 

  • Rossi G, Jiang Y, Newman A, Ferro-Novick S (1991) Dependence of Ypt1 and Sec4 membrane attachment on Bet2. Nature 351:158–161

    Article  PubMed  CAS  Google Scholar 

  • Rothman J, Orci L (1992) Molecular dissection of the secretory pathway. Nature 355:409–415

    Article  PubMed  CAS  Google Scholar 

  • Salminen A, Novick PJ (1987) A ras-like protein is required for a post-Golgi event in yeast secretion. Cell 49:527–538

    Article  PubMed  CAS  Google Scholar 

  • Salminen A, Novick P (1989) The Secl5 protein responds to the function of the GTP binding protein, Sec4, to control vesicular traffic in yeast. J Cell Biol 109:1023–1036

    Article  PubMed  CAS  Google Scholar 

  • Sasaki T, Kikuchi A, Araki S, Hata Y, Isomura M, Kuroda S, Takai Y (1990) Purification and characterization from bovine brain cytosol of a protein that inhibits dissociation of the GDP form and the subsequent binding of GTP to smg p25A, a ras p21-like GTP-binding protein. J Biol Chem 265:2333–2337

    PubMed  CAS  Google Scholar 

  • Sasaki T, Kaibuchi K, Kabcenell AK, Novick PJ, Takai Y (1991) A mammalian inhibitory GDP/GTP exchange protein (GDP Dissociation Inhibitor) for smg p25A is active on the yeast SEC4 protein. Mol Cell Biol 11:2909–2912

    PubMed  CAS  Google Scholar 

  • Segev N (1991) Mediation of the attachment or fusion step in vesicular transport by the GTP-binding Ypt1 protein. Science 252:1553–1556

    Article  PubMed  CAS  Google Scholar 

  • Segev N, Mulholland J, Bostein D (1988) The yeast GTP-binding YPT1 protein and a mamalian counterpart are associated with the secretion machinery. Cell 52:915–924

    Article  PubMed  CAS  Google Scholar 

  • Tanaka K, Nakafuku M, Satoh T, Marshall MS, Gibbs JB, Matsumoto K, Kaziro Y, Tohe A (1990) S. cerevisiae genes IRA1 and IRA2 encode protiens that may be functionally equivalent to mammalian ras GTPase activation protein. Cell 60:803–807

    Article  PubMed  CAS  Google Scholar 

  • Toda T, Uno I, Ishikawa T, Powers S, Kataoka T, Broek D, Cameron S, Broach J, Matsumoto K, Wigler M (1985) In yeast, RAS proteins are controlling elements of the adenylate cyclase. Cell 40:27–36

    Article  PubMed  CAS  Google Scholar 

  • Touchot N, Chardin P, Tavitian A (1987) Four additional membranes of the ras gene superfamily isolated by an oligonucleotide strategy: molecular cloning of YPT-related cDNAs from a rat btain library. Proc Natl Acad Sci USA 84:8210–8214

    Article  PubMed  CAS  Google Scholar 

  • Trahey M, McCormick F (1987) A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants. Science 238:542–545

    Article  PubMed  CAS  Google Scholar 

  • Ueda T, Kikuchi A, Ohga N, Yamamoto J, Takai Y (1990) Purification and characterization from bovine brain cytosol of a novel regulatory protein inhibiting the dissociation of GDP from and the subsequent binding of GTP to rhoB p20, a ras p21-like GTP-binding protein. J Biol Chem 265:9373–9380

    PubMed  CAS  Google Scholar 

  • Van der Sluijs P, Hull M, Zahraoui A, Tavitian A, Goud B, Mellman I (1991) The small GTP-binding protein rab4 is associated with early endosomes. Proc Natl Acad Sci USA 88:6313–6317

    Article  Google Scholar 

  • Walworth NC, Goud B, Kabcenell AK, Novick PJ (1989) Mutational analysis of SEC4 suggests a cyclical mechanism for the regulation of vesicular traffic. Cell 8:1685–1693

    CAS  Google Scholar 

  • Walworth NC, Brennwald P, Kabcenell AK, Garrett M, Novick P (1992) Hydrolysis of GTP by Sec4 protein plays an important role in vesicular transport and is stimulated by a GTPase activating protein in yeast. Mol Cell Biol 12:2017–2028

    PubMed  CAS  Google Scholar 

  • Zahraoui A, Touchot N, Chardin P, Tavitian A (1989) The human Rab genes encode a family of GTP-binding proteins related to yeast YPT1 and SEC4 products involved in secretion. J Biol Chem 264:12394–12401

    PubMed  CAS  Google Scholar 

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  1. P. Novick
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  2. P. Brennwald
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Editors and Affiliations

  1. Department of Medicine, Cell Biology and Experimental Therapeutics, Room 3C-385, Houston VA Medical Center, Baylor College of Medicine, 2002 Holcombe Boulevard, Houston, TX, 77030, USA

    Burton F. Dickey M.D.

  2. Department of Cell Biology, Molecular Physiology and Biophysics, Medicine and Neurosciences, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    Lutz Birnbaumer Ph.D.

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© 1993 Springer-Verlag Berlin Heidelberg

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Novick, P., Brennwald, P. (1993). Small GTPases and Vesicle Trafficking: Sec4p and its Interaction with Up- and Downstream Elements. In: Dickey, B.F., Birnbaumer, L. (eds) GTPases in Biology I. Handbook of Experimental Pharmacology, vol 108 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78267-1_4

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  • DOI: https://doi.org/10.1007/978-3-642-78267-1_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-78269-5

  • Online ISBN: 978-3-642-78267-1

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