• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Nov 15, 1994; 13(22): 5262–5273.
PMCID: PMC395482

Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes.


Rab proteins comprise a family of small GTPases that serve a regulatory role in vesicular membrane traffic. Geranylgeranylation of these proteins on C-terminal cysteine motifs is crucial for their membrane association and function. This post-translational modification is catalysed by rab geranylgeranyl transferase (Rab-GGTase), a multisubunit enzyme consisting of a catalytic heterodimer and an accessory component, named rab escort protein (REP)-1. Previous in vitro studies have suggested that REP-1 presents newly synthesized rab proteins to the catalytic component of the enzyme, and forms a stable complex with the prenylated proteins following the transfer reaction. According to this model, a cellular factor would be required to dissociate the rab protein from REP-1 and to allow it to recycle in the prenylation reaction. RabGDP dissociation inhibitor (RabGDI) was considered an ideal candidate for this role, given its established function in mediating membrane association of prenylated rab proteins. Here we demonstrate that dissociation from REP-1 and binding of rab proteins to the membrane do not require RabGDI or other cytosolic factors. The mechanism of REP-1-mediated membrane association of rab5 appears to be very similar to that mediated by RabGDI. Furthermore, REP-1 and RabGDI share several other functional properties, the ability to inhibit the release of GDP and to remove rab proteins from membranes; however, RabGDI cannot assist in the prenylation reaction. These data suggest that REP-1 is per se sufficient to chaperone newly prenylated rab proteins to their target membranes.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Andres DA, Seabra MC, Brown MS, Armstrong SA, Smeland TE, Cremers FP, Goldstein JL. cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein. Cell. 1993 Jun 18;73(6):1091–1099. [PubMed]
  • Araki S, Kikuchi A, Hata Y, Isomura M, Takai Y. 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. 1990 Aug 5;265(22):13007–13015. [PubMed]
  • Araki S, Kaibuchi K, Sasaki T, Hata Y, Takai Y. Role of the C-terminal region of smg p25A in its interaction with membranes and the GDP/GTP exchange protein. Mol Cell Biol. 1991 Mar;11(3):1438–1447. [PMC free article] [PubMed]
  • Armstrong J. Two fingers for membrane traffic. Curr Biol. 1993 Jan;3(1):33–35. [PubMed]
  • Armstrong SA, Seabra MC, Südhof TC, Goldstein JL, Brown MS. cDNA cloning and expression of the alpha and beta subunits of rat Rab geranylgeranyl transferase. J Biol Chem. 1993 Jun 5;268(16):12221–12229. [PubMed]
  • Beranger F, Cadwallader K, Porfiri E, Powers S, Evans T, de Gunzburg J, Hancock JF. Determination of structural requirements for the interaction of Rab6 with RabGDI and Rab geranylgeranyltransferase. J Biol Chem. 1994 May 6;269(18):13637–13643. [PubMed]
  • Brennwald P, Novick P. Interactions of three domains distinguishing the Ras-related GTP-binding proteins Ypt1 and Sec4. Nature. 1993 Apr 8;362(6420):560–563. [PubMed]
  • Brown MS, Goldstein JL. Protein prenylation. Mad bet for Rab. Nature. 1993 Nov 4;366(6450):14–15. [PubMed]
  • Bucci C, Parton RG, Mather IH, Stunnenberg H, Simons K, Hoflack B, Zerial M. The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell. 1992 Sep 4;70(5):715–728. [PubMed]
  • Bucci C, Wandinger-Ness A, Lütcke A, Chiariello M, Bruni CB, Zerial M. Rab5a is a common component of the apical and basolateral endocytic machinery in polarized epithelial cells. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5061–5065. [PMC free article] [PubMed]
  • Carlsson SR, Roth J, Piller F, Fukuda M. Isolation and characterization of human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Major sialoglycoproteins carrying polylactosaminoglycan. J Biol Chem. 1988 Dec 15;263(35):18911–18919. [PubMed]
  • Chavrier P, Gorvel JP, Stelzer E, Simons K, Gruenberg J, Zerial M. Hypervariable C-terminal domain of rab proteins acts as a targeting signal. Nature. 1991 Oct 24;353(6346):769–772. [PubMed]
  • Cremers FP, van de Pol DJ, van Kerkhoff LP, Wieringa B, Ropers HH. Cloning of a gene that is rearranged in patients with choroideraemia. Nature. 1990 Oct 18;347(6294):674–677. [PubMed]
  • Cremers FP, Molloy CM, van de Pol DJ, van den Hurk JA, Bach I, Geurts van Kessel AH, Ropers HH. An autosomal homologue of the choroideremia gene colocalizes with the Usher syndrome type II locus on the distal part of chromosome 1q. Hum Mol Genet. 1992 May;1(2):71–75. [PubMed]
  • Cremers FP, Armstrong SA, Seabra MC, Brown MS, Goldstein JL. REP-2, a Rab escort protein encoded by the choroideremia-like gene. J Biol Chem. 1994 Jan 21;269(3):2111–2117. [PubMed]
  • Elazar Z, Mayer T, Rothman JE. Removal of Rab GTP-binding proteins from Golgi membranes by GDP dissociation inhibitor inhibits inter-cisternal transport in the Golgi stacks. J Biol Chem. 1994 Jan 14;269(2):794–797. [PubMed]
  • Gorvel JP, Chavrier P, Zerial M, Gruenberg J. rab5 controls early endosome fusion in vitro. Cell. 1991 Mar 8;64(5):915–925. [PubMed]
  • Goud B. Small GTP-binding proteins as compartmental markers. Semin Cell Biol. 1992 Oct;3(5):301–307. [PubMed]
  • Hancock JF, Hall A. A novel role for RhoGDI as an inhibitor of GAP proteins. EMBO J. 1993 May;12(5):1915–1921. [PMC free article] [PubMed]
  • Herz J, Kowal RC, Ho YK, Brown MS, Goldstein JL. Low density lipoprotein receptor-related protein mediates endocytosis of monoclonal antibodies in cultured cells and rabbit liver. J Biol Chem. 1990 Dec 5;265(34):21355–21362. [PubMed]
  • Lombardi D, Soldati T, Riederer MA, Goda Y, Zerial M, Pfeffer SR. Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J. 1993 Feb;12(2):677–682. [PMC free article] [PubMed]
  • Magee T, Newman C. The role of lipid anchors for small G proteins in membrane trafficking. Trends Cell Biol. 1992 Nov;2(11):318–323. [PubMed]
  • Nishimura N, Nakamura H, Takai Y, Sano K. Molecular cloning and characterization of two rab GDI species from rat brain: brain-specific and ubiquitous types. J Biol Chem. 1994 May 13;269(19):14191–14198. [PubMed]
  • Novick P, Brennwald P. Friends and family: the role of the Rab GTPases in vesicular traffic. Cell. 1993 Nov 19;75(4):597–601. [PubMed]
  • Novick P, Garrett MD. Vesicular transport. No exchange without receipt. Nature. 1994 May 5;369(6475):18–19. [PubMed]
  • Nuoffer C, Davidson HW, Matteson J, Meinkoth J, Balch WE. A GDP-bound of rab1 inhibits protein export from the endoplasmic reticulum and transport between Golgi compartments. J Cell Biol. 1994 Apr;125(2):225–237. [PMC free article] [PubMed]
  • Peter M, Chavrier P, Nigg EA, Zerial M. Isoprenylation of rab proteins on structurally distinct cysteine motifs. J Cell Sci. 1992 Aug;102(Pt 4):857–865. [PubMed]
  • Pfeffer SR. GTP-binding proteins in intracellular transport. Trends Cell Biol. 1992 Feb;2(2):41–46. [PubMed]
  • Regazzi R, Kikuchi A, Takai Y, Wollheim CB. The small GTP-binding proteins in the cytosol of insulin-secreting cells are complexed to GDP dissociation inhibitor proteins. J Biol Chem. 1992 Sep 5;267(25):17512–17519. [PubMed]
  • Sasaki T, Kikuchi A, Araki S, Hata Y, Isomura M, Kuroda S, Takai Y. Purification and characterization from bovine brain cytosol of a protein that inhibits the dissociation of GDP from and the subsequent binding of GTP to smg p25A, a ras p21-like GTP-binding protein. J Biol Chem. 1990 Feb 5;265(4):2333–2337. [PubMed]
  • Seabra MC, Brown MS, Slaughter CA, Südhof TC, Goldstein JL. Purification of component A of Rab geranylgeranyl transferase: possible identity with the choroideremia gene product. Cell. 1992 Sep 18;70(6):1049–1057. [PubMed]
  • Seabra MC, Goldstein JL, Südhof TC, Brown MS. Rab geranylgeranyl transferase. A multisubunit enzyme that prenylates GTP-binding proteins terminating in Cys-X-Cys or Cys-Cys. J Biol Chem. 1992 Jul 15;267(20):14497–14503. [PubMed]
  • Seabra MC, Brown MS, Goldstein JL. Retinal degeneration in choroideremia: deficiency of rab geranylgeranyl transferase. Science. 1993 Jan 15;259(5093):377–381. [PubMed]
  • Shisheva A, Südhof TC, Czech MP. Cloning, characterization, and expression of a novel GDP dissociation inhibitor isoform from skeletal muscle. Mol Cell Biol. 1994 May;14(5):3459–3468. [PMC free article] [PubMed]
  • Simons K, Zerial M. Rab proteins and the road maps for intracellular transport. Neuron. 1993 Nov;11(5):789–799. [PubMed]
  • Soldati T, Riederer MA, Pfeffer SR. Rab GDI: a solubilizing and recycling factor for rab9 protein. Mol Biol Cell. 1993 Apr;4(4):425–434. [PMC free article] [PubMed]
  • Soldati T, Shapiro AD, Svejstrup AB, Pfeffer SR. Membrane targeting of the small GTPase Rab9 is accompanied by nucleotide exchange. Nature. 1994 May 5;369(6475):76–78. [PubMed]
  • Steele-Mortimer O, Gruenberg J, Clague MJ. Phosphorylation of GDI and membrane cycling of rab proteins. FEBS Lett. 1993 Aug 30;329(3):313–318. [PubMed]
  • Steele-Mortimer O, Clague MJ, Huber LA, Chavrier P, Gruenberg J, Gorvel JP. The N-terminal domain of a rab protein is involved in membrane-membrane recognition and/or fusion. EMBO J. 1994 Jan 1;13(1):34–41. [PMC free article] [PubMed]
  • Stenmark H, Valencia A, Martinez O, Ullrich O, Goud B, Zerial M. Distinct structural elements of rab5 define its functional specificity. EMBO J. 1994 Feb 1;13(3):575–583. [PMC free article] [PubMed]
  • Stenmark H, Parton RG, Steele-Mortimer O, Lütcke A, Gruenberg J, Zerial M. Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis. EMBO J. 1994 Mar 15;13(6):1287–1296. [PMC free article] [PubMed]
  • Takai Y, Kaibuchi K, Kikuchi A, Kawata M. Small GTP-binding proteins. Int Rev Cytol. 1992;133:187–230. [PubMed]
  • Ullrich O, Stenmark H, Alexandrov K, Huber LA, Kaibuchi K, Sasaki T, Takai Y, Zerial M. Rab GDP dissociation inhibitor as a general regulator for the membrane association of rab proteins. J Biol Chem. 1993 Aug 25;268(24):18143–18150. [PubMed]
  • Ullrich O, Horiuchi H, Bucci C, Zerial M. Membrane association of Rab5 mediated by GDP-dissociation inhibitor and accompanied by GDP/GTP exchange. Nature. 1994 Mar 10;368(6467):157–160. [PubMed]
  • Walworth NC, Goud B, Kabcenell AK, Novick PJ. Mutational analysis of SEC4 suggests a cyclical mechanism for the regulation of vesicular traffic. EMBO J. 1989 Jun;8(6):1685–1693. [PMC free article] [PubMed]
  • Zerial M, Stenmark H. Rab GTPases in vesicular transport. Curr Opin Cell Biol. 1993 Aug;5(4):613–620. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Gene
    Gene links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...