Skip to main content
SpringerLink
Log in

Rabs

  • Chapter
The Golgi Apparatus

  • 1390 Accesses

Abstract

In this chapter we will describe the Rab family of proteins, one of the most important molecular machines operating within the secretory pathway. Rab proteins (Ras-related proteins in brain) are evolutionary conserved regulators of membrane traffic. They are of key importance for proper functioning of the exocytic secretory pathway and endocytosis. In fact, Rabs seem to play a role in all events of intracellular transport, i.e. they take part in cargo selection and budding of vesicular (or tubular) structures in donor compartments, they regulate the transport of these membrane-bound structures along cytoskeletal tracks, they control their docking to the target membrane, and they are involved in the final fusion of donor and target membrane. Moreover, they guarantee that organelles keep their protein and lipid composition as well as their right position within the cell (Seabra et al. 2002; Grosshans etal. 2006). Whereas 11 Rabs have been described in Saccharomycescerevisiae, more than 70 Rabs and Rab-like proteins exist in mammals (Pereira-Leal and Seabra 2001; Gurkan et al. 2005). Consequently, together with the SNAREs the Rabs are the largest of the protein families involved in membrane trafficking.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aivazian D, Serrano RL, Pfeffer S (2006) TIP47 isa key effector for Rab9 localization. J Cell Biol 173(6): 917–926

    Article  PubMed  CAS  Google Scholar 

  • Ali BR, Wasmeier C, Lamoreux L, Strom M, Seabra MC (2004) Multiple regions contribute to membrane targeting of Rab GTPases. J Cell Sci 117(Pt 26): 6401–6412

    Article  PubMed  CAS  Google Scholar 

  • Allan BB, Moyer BD, Balch WE (2002) Rabl recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion. Science 289(5478): 444–448

    Article  Google Scholar 

  • Alory C, Balch WE (2001) Organization of the Rab-GDI/CHM superfamily: the functional basis for choroideremia disease. Traffic 2(8): 532–543

    Article  PubMed  CAS  Google Scholar 

  • Alory C, Balch WE (2003) Molecular evolution of the Rab-escort-protein/guanine-nucleotide-dissociation-inhibitor superfamily. Mol Biol Cell 14: 3857–3867

    Article  PubMed  CAS  Google Scholar 

  • An Y, Shao Y, Alory C, Matteson J, Sakisaka T, Chen W, Gibbs RA, Wilson IA, Balch WE (2003) Geranylgeranyl switching regulates GDI-Rab GTPase recycling. Structure 11: 347–357

    Article  PubMed  CAS  Google Scholar 

  • Babbey CM, Ahktar N, Wang E, Chen CC, Grant BD, Dunn KW (2006) Rab10 regulates membrane transport through early endosomes of polarized Madin-Darby canine kidney cells. Mol Biol Cell 17(7): 3156–3175

    Article  PubMed  CAS  Google Scholar 

  • Barbero P, Bittova L, Pfeffer SR (2002) Visualization of Rab9-mediated vesicle transport from endosomes to the trans-Golgi in living cells. J Cell Biol 156(3): 511–518

    Article  PubMed  CAS  Google Scholar 

  • Bernards A (2003) GAPs galore! A survey of putative Ras superfamily GTPase activating proteins in man and Drosophila. Biochim Biophys Acta 1603(2): 47–82

    PubMed  CAS  Google Scholar 

  • Beard M, Satoh A, Shorter J, Warren GA (2005) Cryptic Rab1-binding site in the p115 tethering protein. J Biol Chem 280(27): 25840–25848

    Article  PubMed  CAS  Google Scholar 

  • Bos JL, Rehmann H, Wittinghofer A (2007) GEFs and GAPs: critical elements in the control of small G proteins. Cell 129(5): 865–877

    Article  PubMed  CAS  Google Scholar 

  • Cai H, Reinisch K, Ferro-Novick S (2007) Coats tethers, Rabs and SNAREs work together to mediate the intracellular destination of a transport vesicle. Dev Cell 12(5): 671–682

    Article  PubMed  CAS  Google Scholar 

  • Carroll KS, Hanna J, Simon I, Krise J, Barbero P, Pfeffer SR (2001) Role of Rab9 GTPase in facilitating receptor recruitment by TIP47. Science 292(5520): 1373–1376

    Article  PubMed  CAS  Google Scholar 

  • Chavrier P, Gorvel JP, Stelzer E, Simons K, Gruenberg J, Zerial M (1991) Hypervariable C-terminal domain of rab proteins acts as a targeting signal. Nature 353(6346): 769–772

    Article  PubMed  CAS  Google Scholar 

  • Constantinescu AT, Rak A, Alexandrov K, Esters H, Goody RS, Scheidig AJ (2002) Rab-subfamily-specific regions of Ypt7p are structurally different from other RabGT-Pases. Structure 10(4): 569–579

    Article  PubMed  CAS  Google Scholar 

  • Desnos C, Schonn JS, Huet S, Tran VS, El-Amraoui A, Raposo G, Fanget I, Chapuis C, Ménasché G, De Saint Basile G, Petit C, Cribier S, Henry JP, Darchen F (2003) Rab27A and its effector MyRIP link secretory granules to F-actin and control their motion towards release sites. J Cell Biol 163(3): 559–570

    Article  PubMed  CAS  Google Scholar 

  • Dirac-Svejstrup AB, Sumizawa T, Pfeffer SR (1997) Identification of a GDI displacement factor that releases endosomal Rab GTPases from Rab-GDI EMBO J 16(3): 465–472

    Article  PubMed  CAS  Google Scholar 

  • Dumas JJ, Zhu Z, Connolly JL, Lambright DG (1999) Structural basis of activation and GTP hydrolysis in Rab proteins. Structure 15: 413–423

    Article  Google Scholar 

  • El-Amraoui A, Schonn JS, Kussel-Andermann P, Blanchard S, Desnos C, Henry JP, Wolfrum U, Darchen F, Petit C (2002) MyRIP, a novel Rab effector, enables myosin VIIa recruitment to retinal melanosomes. EMBO Rep 3(5): 463–470

    Article  PubMed  CAS  Google Scholar 

  • Fuchs E, Haas AK, Spooner RA, Yoshimura S, Lord JM, Barr FA (2007) Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways. J Cell Biol 177: 1133–1143

    Article  PubMed  CAS  Google Scholar 

  • Fukuda M, Kuroda TS, Mikoshiba K (2002) Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport. J Biol Chem 277(14): 12432–12436

    Article  PubMed  CAS  Google Scholar 

  • Gibbs D, Azarian SM, Lillo C, Kitamoto J, Klomp AE, Steel KP, Libby RT, Williams DS (2004) Role of myosin VIIa and Rab27a in the motility and localization of RPE melanosomes. J Cell Sci 117(Pt26): 6473–6483

    Article  PubMed  CAS  Google Scholar 

  • Grosshans BL, Ortiz D, Novick P (2006) Rabs and their effectors: achieving specificity in membrane traffic. Proc Natl Acad Sci USA 103(32): 11821–11827

    Article  PubMed  CAS  Google Scholar 

  • Guo W, Roth D, Walch-Solimena C, Novick P (1999) The exocyst is an effector for Sec4p, targeting secretory vesicles to sites of exocytosis. EMBO J 18(4): 1071–1080

    Article  PubMed  CAS  Google Scholar 

  • Gurkan C, Lapp H, Alory C, Su AI, Hogenesch J, Balch WE (2005) Large-scale profiling of Rab GTPase trafficking networks: the membrome. Mol Biol Cell 16: 3847–3864

    Article  PubMed  CAS  Google Scholar 

  • Hannah MJ, Hume AN, Arribas M, Williams R, Hewlett LJ, Seabra MC and Cutler DF (2003) Weibel-Palade bodies recruit Rab27 by a content-driven, maturation-dependent mechanism that is independent of cell type. J Cell Sci 116: 3939–3948

    Article  PubMed  CAS  Google Scholar 

  • Jiang S, Storrie B (2005) Cisternal rab proteins regulate Golgi apparatus redistribution in response to hypotonic stress. Mol Biol Cell 16(5): 2586–2596

    Article  PubMed  CAS  Google Scholar 

  • Luan P, Heine A, Zeng K, Moyer B, Greasely SE, Kuhn P, Balch WE, Wilson IA (2000) A new functional domain of guanine nucleotide dissociation inhibitor (alpha-GDI) involved in Rab recycling. Traffic 1(3): 270–281

    Article  PubMed  CAS  Google Scholar 

  • Merithew E, Hatherly S, Dumas JJ, Lawe DC, Heller-Harrison R, Lambright DG (2001) Structural plasticity of an invariant hydrophobic triad in the switch regions of Rab GTPases is a determinant of effector recognition. J Biol Chem 276(17): 13982–13988

    PubMed  CAS  Google Scholar 

  • Moyer BD, Allan BB, Balch WE (2001) Rabl interaction with a GM130 effector complex regulates COPII vesicle cis-Golgi tethering. Traffic 2(4): 268–276

    Article  PubMed  CAS  Google Scholar 

  • Nagashima K, Torii S, Yi Z, Igarashi M, Okamoto K, Takeuchi T, Izumi T (2002) Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions. FEBS Lett 517(1–3): 233–238

    Article  PubMed  CAS  Google Scholar 

  • Nishimura N, Nakamura H, Takai Y, Sano K (1994) Molecular cloning and characterization of two rab GDI species from rat brain: brain-specific and ubiquitous types. J Biol Chem 269: 14191–14198

    PubMed  CAS  Google Scholar 

  • Oberhauser AF, Monck JR, Balch WE, Fernandez JM (1992) Exocytotic fusion is activated by Rab3a peptides. Nature 360(6401): 270–273

    Article  PubMed  CAS  Google Scholar 

  • Ortiz D, Medkova M, Walch-Solimena C, Novick P (2002) Ypt32 recruits the Sec4p guanine nucleotide exchange factor, Sec2p, to secretory vesicles; evidence for a Rab cascade in yeast. J Cell Biol 157: 1005–1015

    Article  PubMed  CAS  Google Scholar 

  • Pasqualato S, Senic-Matuglia F, Renault L, Goud B, Salamero J, Cherfils J (2004) The structural GDP/GTP cycle of Rab 11 reveals a novel interface involved in the dynamics of recycling endosomes. J Biol Chem 279(12): 11480–11488

    Article  PubMed  CAS  Google Scholar 

  • Pelkmans L, Burli T, Zerial M, Helenius A (2004) Caveolin-stabilized membrane domains as multifunctional transport and sorting devices in endocytic membrane traffic. Cell 118(6): 767–780

    Article  PubMed  CAS  Google Scholar 

  • Peräanen J, Auvinen P, Virta H, Wepf R, Simons K (1996) Rab8 promotes polarized membrane transport through reorganization of actin and microtubules in fibroblasts. J Cell Biol 135(1): 153–167

    Article  CAS  Google Scholar 

  • Pereira-Leal JB, Hume AN, Seabra MC (2001) Prenylation of Rab GTPases: molecular mechanisms and involvement in genetic disease. FEBS Lett 498: 197–200

    Article  PubMed  CAS  Google Scholar 

  • Pereira-Leal J, Seabra MC (2000) The mammalian Rab family of small GTPases: definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily. J Mol Biol 301: 1077–1087

    Article  PubMed  CAS  Google Scholar 

  • Pereira-Leal JB, Seabra MC (2001) Evolution of the Rab family of small GTP-binding proteins. J Mol Biol 313(4): 889–901

    Article  PubMed  CAS  Google Scholar 

  • Pfeffer SR (2005) Structural clues to Rab GTPase functional diversity. J Biol Chem 280(16): 15485–15488

    Article  PubMed  CAS  Google Scholar 

  • Pfeffer SR (2007) Unsolved mysteries in membrane traffic. Annu Rev Biochem 76: 629–645

    Article  PubMed  CAS  Google Scholar 

  • Pfeffer S, Aivazian D (2004) Targeting Rab GTPases to distinct membrane compartments. Nat Rev Mol Cell Biol 5(11): 886–896

    Article  PubMed  CAS  Google Scholar 

  • Pylypenko O, Rak A, Reents R, Niculae A, Sidorovitch V, Cioaca MD, Bessolitsyna E, Thoma NH, Waldmann H, Schlichting I, Goody RS, Alexandrov K (2003) Structure of Rab escort protein-1 in complex with Rab geranylgeranyltransf erase. Mol Cell 11(2): 483–494

    Article  PubMed  CAS  Google Scholar 

  • Pylypenko O, Rak A, Durek T, Kushnir S, Dursina BE, Thomae NH, Constantinescu AT, Brunsveld L, Watzke A, Waldmann H, Goody RS, Alexandrov K (2006) Structure of doubly prenylated Ypt1: GDI complex and the mechanism of GDI-mediated Rab recycling. EMBO J 11: 13–23

    Article  Google Scholar 

  • Rink J, Ghigo E, Kalaidzidis Y, Zerial M (2005) Rab conversion as a mechanism of progression from early to late endosomes. Cell 122(5): 735–749

    Article  PubMed  CAS  Google Scholar 

  • Saraste J, Latineen U, Goud B (1995) Localization of the small GTP-binding protein rab1 p to early compartments of the secretory pathway. J Cell Sci 108(Pt4): 1541–1552

    PubMed  CAS  Google Scholar 

  • Schalk I, Zeng K, Wu SK, Stura EA, Matteson J, Huang M, Tandon A, Wilson IA, Balch WE (1996) Structure and mutational analysis of Rab GDP-dissociation inhibitor. Nature 381:42–48

    Article  PubMed  CAS  Google Scholar 

  • Schwartz S, Cao C, Pylypenko O, Rak A, Wandinger-Ness A (2007) Rab GTPases at a glance. J Cell Sci 120(Pt 22): 3905–3910

    Article  PubMed  CAS  Google Scholar 

  • Seabra MC, Mules EH, Hume AN (2002) Rab GTPases intracellular traffic and disease. Trends Mol Med 8(1): 23–30

    Article  PubMed  CAS  Google Scholar 

  • Segev N (2001) Ypt and Rab GTPases: insight into functions through novel interactions. Curr Opin Cell Biol 13(4): 500–511

    Article  PubMed  CAS  Google Scholar 

  • Shorter J, Beard MB, Seemann J, Dirac-Svejstrup AB, Warren G (2002) Sequential tethering of Golgins and catalysis of SNAREpin assembly by the vesicle-tethering protein p115. J Cell Biol 157(1): 45–62

    Article  PubMed  CAS  Google Scholar 

  • Sivars U, Aivazian D, Pfeffer SR (2003) Yip3 catalyses the dissociation of endosomal Rab-GDI complexes. Nature 425: 856–859

    Article  PubMed  CAS  Google Scholar 

  • Sonnichsen B, De Renzis S, Nielsen E, Rietdorf J, Zerial M (2000) Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5, and Rab11. J Cell Biol 149(4): 901–914

    Article  PubMed  CAS  Google Scholar 

  • Stenmark H, Valencia A, Martinez O, Ullrich O, Goud B, Zerial M (1994) Distinct structural elements of rab5 define its functional specificity. EMBO J 13: 575–583

    PubMed  CAS  Google Scholar 

  • Stinchcombe JC, Barral DC, Mules EH, Booth S, Hume AN, Machesky LM, Seabra MC, Griffiths GM (2001) Rab27a is required for regulated secretion in cytotoxic T lymphocytes. J Cell Biol 152(4): 825–834

    Article  PubMed  CAS  Google Scholar 

  • Strom M, Hume AN, Tarafder AK, Barkagianni E, Seabra MC (2002) A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melano-some transport. J Biol Chem 277(28): 25423–24530

    Article  PubMed  CAS  Google Scholar 

  • Stroupe C, Brunger AT (2000) Crystal structures of a Rab protein in its inactive and active conformations. J Mol Biol 304(4): 585–598

    Article  PubMed  CAS  Google Scholar 

  • Thoma NH, Iakovenko A, Kalinin A, Waldmann H, Goody RS, Alexandrov K (2001) Allosteric regulation of substrate binding and product release in geranylgeranyl transferase type II Biochemistry 40: 268–274

    Article  PubMed  CAS  Google Scholar 

  • Tisdale EJ, Bourne JR, Khosravi-Far R, Der CJ, Balch WE (1992) GTP-binding mutants of Rab1 and Rab2 are potent inhibitors of vesicular transport form the endoplasmic reticulum to the Golgi complex. J Cell Biol 119: 749–761

    Article  PubMed  CAS  Google Scholar 

  • Toikkanen JH, Miller KJ, Soderlund H, Jäantti J, Keräanen S (2003) The beta subunit of the Sec61p endoplasmic reticulum translocon interacts with the exocyst complex in Saccharomyces cerevisiae. J Biol Chem 278(23): 20946–20953

    Article  PubMed  CAS  Google Scholar 

  • Ullrich O, Stenmark H, Alexandrov K, Huber LA, Kaibuchi K, Sasaki T, Takai Y, Zerial M (1993) Rab GDP dissociation inhiband itor as a general regulator for the membrane association of rab proteins. J Biol Chem 268(24): 18143–18150

    PubMed  CAS  Google Scholar 

  • Ullrich O, Reinsch S, Urbe, S, Zerial M, Parton RG (1996) Rab11 regulates recycling through the pericentriolar recycling endosome. J Cell Biol 135(4): 913–924

    Article  PubMed  CAS  Google Scholar 

  • Wennerberg K, Rossman KL, Der CJ (2005) The Ras superfamily at a glance. J Cell Sci 118(Pt 5): 843–846

    Article  PubMed  CAS  Google Scholar 

  • Wilson AL, Erdman RA, Maltese WA (1996) Association of Rab1 B with GDP-dissociation inhibitor (GDI) is required for recycling but not initial membrane targeting of the Rab protein. J Biol Chem 271: 10932–10940

    Article  PubMed  CAS  Google Scholar 

  • Wittmann JG, Rudolph MG (2004) Crystal structure of Rab9 complexed to GDP reveals a dimer with an active conformation of switch II. FEBS Lett 568(1–3): 23–29

    Article  PubMed  CAS  Google Scholar 

  • Wu X, Bowers B, Rao K, Wei Q, Hammer JA III (1998) Visualization of melanosome dynamics within wild-type and dilute melanocytes suggests a paradigm for myosin V function In vivo. J Cell Biol Dec 28;143(7): 1899–1918

    CAS  Google Scholar 

  • Wu YW, Tan KT, Waldmann H, Goody RS, Alexandrov K (2007) Interaction analysis of prenylated Rab GTPase with Rab escort protein and GDP dissociation inhibitor explains the need for both regulators. Proc Natl Acad Sci USA 104(30): 12294–12299

    Article  PubMed  CAS  Google Scholar 

  • Zerial M, McBride H (2001) Rab proteins as membrane organizers. Nat Rev Mol Cell Biol 2(2): 107–117

    Article  PubMed  CAS  Google Scholar 

  • Zhang XM, Ellis S, Sriratana A, Mitchell CA, Rowe T (2004) Sec15 is an effector for the Rab11 GTPase in mammalian cells. J Biol Chem 279(41): 43027–43034

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. BIOQUANT, University of Heidelberg, Im Neuenheimer Feld 267, 69120, Heidelberg, Germany

    Christoph Claas

  2. Laboratory of Intracellular Traffic Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Via Nazionale 8, 66030, S. Maria Imbaro (Chieti), Italy

    Alexander A Mironov

  3. BIOQUANT, University of Heidelberg, Im Neuenheimer Feld 267, 69120, Heidelberg, Germany

    Vytaute Starkuviene

Authors
  1. Christoph Claas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander A Mironov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vytaute Starkuviene
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Cell Biology and Oncology, Consorzio Mario Negri Sud Laboratory of Intracellular Traffic, S. Maria Imbaro (Chieti), Italy

    Alexander A. Mironov

  2. Department of Cell Biology and Ultrastructure Research Institute of Histology and Embryology Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria

    Margit Pavelka

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag/Wien

About this chapter

Cite this chapter

Claas, C., Mironov, A.A., Starkuviene, V. (2008). Rabs. In: Mironov, A.A., Pavelka, M. (eds) The Golgi Apparatus. Springer, Vienna. https://doi.org/10.1007/978-3-211-76310-0_5

Download citation

Publish with us

Policies and ethics

Search

Navigation