rab3 gtp binding proteins


Summary: A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in calcium-dependent EXOCYTOSIS. This enzyme was formerly listed as EC

Top Publications

  1. Geppert M, Bolshakov V, Siegelbaum S, Takei K, De Camilli P, Hammer R, et al. The role of Rab3A in neurotransmitter release. Nature. 1994;369:493-7 pubmed
    ..Rab3A thus appears not to be essential for synaptic vesicle exocytosis but to play a role in the recruitment of synaptic vesicles for exocytosis during repetitive stimulation. ..
  2. Coppola T, Perret Menoud V, Gattesco S, Magnin S, Pombo I, Blank U, et al. The death domain of Rab3 guanine nucleotide exchange protein in GDP/GTP exchange activity in living cells. Biochem J. 2002;362:273-9 pubmed
    ..We propose that the death domain of Rab3-GEP acts as a molecular switch and co-ordinates multiple functions of the protein by exchanging its binding partners. ..
  3. Tanaka M, Miyoshi J, Ishizaki H, Togawa A, Ohnishi K, Endo K, et al. Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction. Mol Biol Cell. 2001;12:1421-30 pubmed
    ..Thus, Rab3 GEP is essential for neurotransmitter release and probably for formation and trafficking of the synaptic vesicles. ..
  4. Geppert M, Goda Y, Stevens C, Sudhof T. The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion. Nature. 1997;387:810-4 pubmed
  5. Darchen F, Zahraoui A, Hammel F, Monteils M, Tavitian A, Scherman D. Association of the GTP-binding protein Rab3A with bovine adrenal chromaffin granules. Proc Natl Acad Sci U S A. 1990;87:5692-6 pubmed
    ..This study suggests that Rab3A, which may also be located on other secretory vesicles containing noncharacterized small GTP-binding proteins, is involved in their biogenesis or in the regulated secretion process. ..
  6. Wada M, Nakanishi H, Satoh A, Hirano H, Obaishi H, Matsuura Y, et al. Isolation and characterization of a GDP/GTP exchange protein specific for the Rab3 subfamily small G proteins. J Biol Chem. 1997;272:3875-8 pubmed
    ..The recombinant protein exhibited GEP activity toward Rab3A, Rab3C, and Rab3D. Northern blot and Western blot analyses indicated that Rab3 GEP was expressed in all the rat tissues examined with the highest expression in brain. ..
  7. Abderrahmani A, Cheviet S, Ferdaoussi M, Coppola T, Waeber G, Regazzi R. ICER induced by hyperglycemia represses the expression of genes essential for insulin exocytosis. EMBO J. 2006;25:977-86 pubmed
  8. Schlüter O, Schmitz F, Jahn R, Rosenmund C, Sudhof T. A complete genetic analysis of neuronal Rab3 function. J Neurosci. 2004;24:6629-37 pubmed
    ..Furthermore, our data demonstrate that Rab3 is not in itself essential for synaptic membrane traffic but functions to modulate the basic release machinery. ..
  9. Weber E, Berta G, Tousson A, St John P, Green M, Gopalokrishnan U, et al. Expression and polarized targeting of a rab3 isoform in epithelial cells. J Cell Biol. 1994;125:583-94 pubmed
    ..The pattern and regulation of rab3B targeting in epithelial cells implicates this monomeric GTPase as a candidate regulator of apical and/or junctional protein traffic in epithelial tissues. ..

More Information


  1. Izumi T, Gomi H, Kasai K, Mizutani S, Torii S. The roles of Rab27 and its effectors in the regulated secretory pathways. Cell Struct Funct. 2003;28:465-74 pubmed
    ..These findings suggest that the Rab27 subfamily regulates various exocytotic pathways using multiple organelle-specific effector proteins. ..
  2. Oishi H, Sasaki T, Nagano F, Ikeda W, Ohya T, Wada M, et al. Localization of the Rab3 small G protein regulators in nerve terminals and their involvement in Ca2+-dependent exocytosis. J Biol Chem. 1998;273:34580-5 pubmed
    ..These results indicate that Rab3 GEP and GAP are colocalized with Rab3A at the synaptic release sites and suggest that they regulate the activity of Rab3A and are involved in Ca2+-dependent exocytosis. ..
  3. Miyoshi J, Takai Y. Dual role of DENN/MADD (Rab3GEP) in neurotransmission and neuroprotection. Trends Mol Med. 2004;10:476-80 pubmed
    ..Recent research supports an important role for DENN/MADD in neuroprotection: reduced endogenous DENN/MADD expression and enhanced pro-apoptotic signalling has been found in brains affected by Alzheimer's disease. ..
  4. Castillo P, Janz R, Sudhof T, Tzounopoulos T, Malenka R, Nicoll R. Rab3A is essential for mossy fibre long-term potentiation in the hippocampus. Nature. 1997;388:590-3 pubmed
    ..Here we show that, although a variety of short-term plasticities are normal, LTP at mossy fibre synapses is abolished in mice lacking the synaptic vesicle protein Rab3A. ..
  5. Chung C, Koprich J, Hallett P, Isacson O. Functional enhancement and protection of dopaminergic terminals by RAB3B overexpression. Proc Natl Acad Sci U S A. 2009;106:22474-9 pubmed publisher
    ..These results suggest that RAB3B improves dopamine handling and storage capacity at presynaptic terminals, and confers protection to vulnerable DA neurons. ..
  6. Iwasaki K, Staunton J, Saifee O, Nonet M, Thomas J. aex-3 encodes a novel regulator of presynaptic activity in C. elegans. Neuron. 1997;18:613-22 pubmed
    ..In C. elegans, aex-3 is expressed in all or nearly all neurons. These results suggest that AEX-3 is a novel regulator of presynaptic activity that interacts with RAB-3 to regulate synaptic vesicle release. ..
  7. Miralles F, Czernichow P, Scharfmann R. Follistatin regulates the relative proportions of endocrine versus exocrine tissue during pancreatic development. Development. 1998;125:1017-24 pubmed
    ..Follistatin could thus represent one of the mesenchymal factors required for the development of the exocrine tissue while exerting a repressive role on the differentiation of the endocrine cells. ..
  8. Regazzi R, Ravazzola M, Iezzi M, Lang J, Zahraoui A, Andereggen E, et al. Expression, localization and functional role of small GTPases of the Rab3 family in insulin-secreting cells. J Cell Sci. 1996;109 ( Pt 9):2265-73 pubmed
    ..Taken together these results indicate an involvement of Rab3A in the control of insulin release in rat and hamster. In human beta-cells, a different Rab3 isoform but with homologous function may replace Rab3A. ..
  9. Baldini G, Hohl T, Lin H, Lodish H. Cloning of a Rab3 isotype predominantly expressed in adipocytes. Proc Natl Acad Sci U S A. 1992;89:5049-52 pubmed
  10. Weber E, Jilling T, Kirk K. Distinct functional properties of Rab3A and Rab3B in PC12 neuroendocrine cells. J Biol Chem. 1996;271:6963-71 pubmed
    ..e. rabphilin-3A. However, these isoforms are functionally distinct monomeric GTPases with Rab3B stimulating a late step in Ca2+-evoked secretion when expressed in PC12 cells. ..
  11. Mahoney T, Liu Q, Itoh T, Luo S, Hadwiger G, Vincent R, et al. Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans. Mol Biol Cell. 2006;17:2617-25 pubmed
  12. Yamaguchi K, Tanaka M, Mizoguchi A, Hirata Y, Ishizaki H, Kaneko K, et al. A GDP/GTP exchange protein for the Rab3 small G protein family up-regulates a postdocking step of synaptic exocytosis in central synapses. Proc Natl Acad Sci U S A. 2002;99:14536-41 pubmed
    ..Because Rab3A reportedly down-regulates Ca(2+)-triggered fusion of synaptic vesicles, these results provide evidence for a role of Rab3 GEP in the postdocking process distinct from Rab3A activation. ..
  13. Rupnik M, Kreft M, Nothias F, Grilc S, Bobanovic L, Johannes L, et al. Distinct role of Rab3A and Rab3B in secretory activity of rat melanotrophs. Am J Physiol Cell Physiol. 2007;292:C98-105 pubmed
    ..These results indicate that Rab3A, but not Rab3B, enhances secretory output from rat melanotrophs and that their function is not redundant. ..
  14. Li L, Chin L. The molecular machinery of synaptic vesicle exocytosis. Cell Mol Life Sci. 2003;60:942-60 pubmed
    ..This review summarizes present knowledge about the molecular mechanisms by which these components mediate and/or regulate synaptic vesicle exocytosis. ..
  15. Millar A, Pavios N, Xu J, Zheng M. Rab3D: a regulator of exocytosis in non-neuronal cells. Histol Histopathol. 2002;17:929-36 pubmed publisher
    ..This review summarises the recent work on the biological function, structural integrity and molecular interactions of Rab3D in non-neuronal cells. ..
  16. Staunton J, Ganetzky B, Nonet M. Rabphilin potentiates soluble N-ethylmaleimide sensitive factor attachment protein receptor function independently of rab3. J Neurosci. 2001;21:9255-64 pubmed
    ..These synergistic interactions were independent of rab3 function and were not observed in rab3-SNARE double mutants. Our data reveal rab3-independent functions for rabphilin in the potentiation of SNARE function. ..
  17. Fukuda M. Synaptotagmin-like protein (Slp) homology domain 1 of Slac2-a/melanophilin is a critical determinant of GTP-dependent specific binding to Rab27A. J Biol Chem. 2002;277:40118-24 pubmed
    ..Based on these findings, I propose that SHD1 of the Slp and Slac2 families be referred to as RBD27 (Rab-binding domain specific for Rab27 isoforms). ..
  18. Sedlacek Z, Korn B, Konecki D, Siebenhaar R, Coy J, Kioschis P, et al. Construction of a transcription map of a 300 kb region around the human G6PD locus by direct cDNA selection. Hum Mol Genet. 1993;2:1865-9 pubmed
    ..The analysis of region-specific cDNA sublibraries represents a simple, rapid and efficient tool for the generation of a regional transcription map. ..
  19. Batusic D, Cimica V, Chen Y, Tron K, Hollemann T, Pieler T, et al. Identification of genes specific to "oval cells" in the rat 2-acetylaminofluorene/partial hepatectomy model. Histochem Cell Biol. 2005;124:245-60 pubmed
    ..We postulate that Ear-2 and Rab-3b may represent novel regulatory factors specifically activated in "oval cells". ..
  20. Graf E, Daniels R, Burgess R, Schwarz T, DiAntonio A. Rab3 dynamically controls protein composition at active zones. Neuron. 2009;64:663-77 pubmed publisher
    ..While previous studies of Rab3 have focused on its role in the synaptic vesicle cycle, these findings demonstrate an additional and unexpected function for Rab3 in the localization of presynaptic proteins to active zones. ..
  21. Kawabe H, Sakisaka T, Yasumi M, Shingai T, Izumi G, Nagano F, et al. A novel rabconnectin-3-binding protein that directly binds a GDP/GTP exchange protein for Rab3A small G protein implicated in Ca(2+)-dependent exocytosis of neurotransmitter. Genes Cells. 2003;8:537-46 pubmed
    ..These results indicate that rabconnectin-3 consists of the alpha and beta subunits and binds directly Rab3 GEP through the beta subunit and indirectly Rab3 GAP through an unidentified molecule(s). ..
  22. Weimer R, Jorgensen E. Controversies in synaptic vesicle exocytosis. J Cell Sci. 2003;116:3661-6 pubmed
  23. Evrard C, Rouget P. Subcellular localization of neural-specific NPDC-1 protein. J Neurosci Res. 2005;79:747-55 pubmed
    ..Although NPDC-1 bound Rab3 GEP in vitro, it seems unlikely to be involved in Ca2+-dependent exocytosis and, thus, in synaptic vesicle trafficking. ..
  24. Mittelstaedt T, Alvaréz Baron E, Schoch S. RIM proteins and their role in synapse function. Biol Chem. 2010;391:599-606 pubmed publisher
    ..Here, we summarize recent findings about the specific roles of the various RIM isoforms in basic synaptic vesicle release as well as long- and short-term presynaptic plasticity. ..
  25. Carroll K, Ray K, Helm B, Carey E. Two-dimensional electrophoresis reveals differential protein expression in high- and low-secreting variants of the rat basophilic leukaemia cell line. Electrophoresis. 2000;21:2476-86 pubmed
    ..The sensitivity of this complementary approach facilitated the detection of some GTP binding and Rab3 proteins, whose expression was not evident in silver-stained 2-D gels. ..
  26. Viggeswarapu M, Wildey G. Cloning and tissue expression of the rat RAB 3C GTP-binding protein. Biochem Biophys Res Commun. 1996;227:645-50 pubmed
    ..Northern blot analyses using probes containing coding and noncoding sequences of the rat rab 3C clone hybridized to a 9.5 kb transcript in brain, adrenal gland, and pituitary RNA pools. ..
  27. Li C, Takei K, Geppert M, Daniell L, Stenius K, Chapman E, et al. Synaptic targeting of rabphilin-3A, a synaptic vesicle Ca2+/phospholipid-binding protein, depends on rab3A/3C. Neuron. 1994;13:885-98 pubmed
    ..These results suggest that analogous to the membrane recruitment of raf by ras, rab3A and rab3C may function in recruiting rabphilin-3A to the synaptic vesicle membrane in a GTP-dependent manner. ..
  28. Sakisaka T, Meerlo T, Matteson J, Plutner H, Balch W. Rab-alphaGDI activity is regulated by a Hsp90 chaperone complex. EMBO J. 2002;21:6125-35 pubmed
  29. Evans C, Williams O, Tuvim M, Nigam R, Mixides G, Blackburn M, et al. Mucin is produced by clara cells in the proximal airways of antigen-challenged mice. Am J Respir Cell Mol Biol. 2004;31:382-94 pubmed
    ..Thus, Clara cells show great plasticity in structure and secretory products, yet have molecular and functional continuity in their identity as specialized apical secretory cells. ..
  30. Oberhauser A, Balan V, Fernandez Badilla C, Fernandez J. RT-PCR cloning of Rab3 isoforms expressed in peritoneal mast cells. FEBS Lett. 1994;339:171-4 pubmed
    ..These products were cloned and sequenced. We have found clones containing sequences that had a 100% homology at the deduced amino acid level to a portion of Rab3B and Rab3D (amino acids 16 to 83). ..
  31. Han S, Park D, Park S, Hong S. Identification of Rab6 as an N-ethylmaleimide-sensitive fusion protein-binding protein. Biochem J. 2000;352 Pt 1:165-73 pubmed
    ..Taken together, we propose a model in which Rab can form an ATP hydrolysis-regulated complex with NSF, and function as a signalling molecule to deliver the signal of vesicle fusion through the interaction with NSF. ..
  32. Baldini G, Wang G, Weber M, Zweyer M, Bareggi R, Witkin J, et al. Expression of Rab3D N135I inhibits regulated secretion of ACTH in AtT-20 cells. J Cell Biol. 1998;140:305-13 pubmed
    ..We conclude that expression of Rab3D N135I specifically impairs late membrane trafficking events necessary for ACTH hormone secretion. ..
  33. von Schantz C, Saharinen J, Kopra O, Cooper J, Gentile M, Hovatta I, et al. Brain gene expression profiles of Cln1 and Cln5 deficient mice unravels common molecular pathways underlying neuronal degeneration in NCL diseases. BMC Genomics. 2008;9:146 pubmed publisher
    ..Since CLN1 and CLN5 code for proteins with distinct functional roles these data may have implications for other forms of NCLs as well. ..
  34. Schoch S, Mittelstaedt T, Kaeser P, Padgett D, Feldmann N, Chevaleyre V, et al. Redundant functions of RIM1alpha and RIM2alpha in Ca(2+)-triggered neurotransmitter release. EMBO J. 2006;25:5852-63 pubmed
    ..Our data thus demonstrate that alpha-RIMs are not essential for synapse formation or synaptic exocytosis, but are required for normal Ca(2+)-triggering of exocytosis. ..
  35. Dalfo E, Barrachina M, Rosa J, Ambrosio S, Ferrer I. Abnormal alpha-synuclein interactions with rab3a and rabphilin in diffuse Lewy body disease. Neurobiol Dis. 2004;16:92-7 pubmed
    ..Since, alpha-synuclein, rab3a and rabphilin participate in the docking and fusion of synaptic vesicles, it can be suggested that exocytosis of neurotransmitters may be impaired in LB diseases. ..
  36. Wang Y, Sugita S, Sudhof T. The RIM/NIM family of neuronal C2 domain proteins. Interactions with Rab3 and a new class of Src homology 3 domain proteins. J Biol Chem. 2000;275:20033-44 pubmed
    ..With the RIM-BPs, we have identified a partner for RIMs that may bind to RIMs at the synapse in addition to Rab3. ..
  37. Pombo I, Martin Verdeaux S, Iannascoli B, Le Mao J, Deriano L, Rivera J, et al. IgE receptor type I-dependent regulation of a Rab3D-associated kinase: a possible link in the calcium-dependent assembly of SNARE complexes. J Biol Chem. 2001;276:42893-900 pubmed
    ..The phosphorylation of syntaxin 4 decreased its binding to its partner SNAP23. Thus, we propose a novel phosphorylation-dependent mechanism by which Rab3D controls SNARE assembly in a calcium-dependent manner. ..
  38. Xu X, Wes P, Chen H, Li H, Yu M, Morgan S, et al. Retinal targets for calmodulin include proteins implicated in synaptic transmission. J Biol Chem. 1998;273:31297-307 pubmed
    ..Thus, it appears that calmodulin functions as a Ca2+ sensor for a broad diversity of retinal proteins, some of which are implicated in synaptic transmission. ..
  39. Schalk I, Zeng K, Wu S, Stura E, Matteson J, Huang M, et al. Structure and mutational analysis of Rab GDP-dissociation inhibitor. Nature. 1996;381:42-8 pubmed
    ..The two most sequence-conserved regions, which form a compact structure at the apex of GDI, are shown by site-directed mutagenesis to play a critical role in the binding of Rab proteins. ..
  40. van Vlijmen T, Vleugel M, Evers M, Mohammed S, Wulf P, Heck A, et al. A unique residue in rab3c determines the interaction with novel binding protein Zwint-1. FEBS Lett. 2008;582:2838-42 pubmed publisher
    ..We also found that SNAP25 bound to the same region in Zwint-1 as rab3c, suggesting a new role for the kinetochore protein Zwint-1 in presynaptic events that are regulated by rab3 and SNAP25. ..
  41. Koushika S, Richmond J, Hadwiger G, Weimer R, Jorgensen E, Nonet M. A post-docking role for active zone protein Rim. Nat Neurosci. 2001;4:997-1005 pubmed
    ..These data suggest Rim acts after vesicle docking likely via regulating priming. ..
  42. Huang Z, Ritter C, Brown A, Finch J, Abu Amer Y, Ross P, et al. Cloning and localization of Rab3 isoforms in bovine, rat, and human parathyroid glands. Biochem Biophys Res Commun. 1999;255:645-51 pubmed
    ..Altogether, our results demonstrate that Rab3 isoforms are expressed in parathyroid chief cells, suggesting that they may play a role in regulated exocytosis in these cells. ..
  43. Darna M, Schmutz I, Richter K, Yelamanchili S, Pendyala G, Höltje M, et al. Time of day-dependent sorting of the vesicular glutamate transporter to the plasma membrane. J Biol Chem. 2009;284:4300-7 pubmed publisher
    ..We conclude that VGLUTs are sorted diurnally to the plasma membrane to modulate glutamate transmission during a day/night cycle, whereas VGAT expression is not oscillating but is increased in the presence of a light/dark cycle. ..
  44. Graham M, Handley M, Barclay J, Ciufo L, Barrow S, Morgan A, et al. A gain-of-function mutant of Munc18-1 stimulates secretory granule recruitment and exocytosis and reveals a direct interaction of Munc18-1 with Rab3. Biochem J. 2008;409:407-16 pubmed
  45. Coppola T, Magnin Luthi S, Perret Menoud V, Gattesco S, Schiavo G, Regazzi R. Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin. J Biol Chem. 2001;276:32756-62 pubmed
    ..We propose that the Rab3 effector RIM is a scaffold protein that participates through its multiple binding partners in the docking and fusion of secretory vesicles at the release sites. ..
  46. Araki K, Nakanishi H, Hirano H, Kato M, Sasaki T, Takai Y. Purification and characterization of Rab GDI beta from rat brain. Biochem Biophys Res Commun. 1995;211:296-305 pubmed
  47. Han J, Lee C, Cheang Y, Kaang B. Suppression of long-term facilitation by Rab3-effector protein interaction. Brain Res Mol Brain Res. 2005;139:13-22 pubmed
    ..In conclusion, our data suggest that apRab3 may act as a negative clamp of LTF through the interaction with effector protein(s), possibly Rim. ..
  48. Sasamura T, Kobayashi T, Kojima S, Qadota H, Ohya Y, Masai I, et al. Molecular cloning and characterization of Drosophila genes encoding small GTPases of the rab and rho families. Mol Gen Genet. 1997;254:486-94 pubmed
    ..The DrhoA and Dcdc42 genes complemented S. cerevisiae rho1 and cdc42 mutations in the same manner as human rhoA and CDC42, respectively. These results suggest functional similarity between Drosophila and mammalian small GTPase genes. ..
  49. Evans E, Zhang W, Jerdeva G, Chen C, Chen X, Hamm Alvarez S, et al. Direct interaction between Rab3D and the polymeric immunoglobulin receptor and trafficking through regulated secretory vesicles in lacrimal gland acinar cells. Am J Physiol Cell Physiol. 2008;294:C662-74 pubmed publisher
    ..These data suggest that the novel localization of pIgR to the regulated secretory pathway of LGACs and its secretion therefrom may be affected by its novel interaction with Rab3D...
  50. Scott G, Zhao Q. Rab3a and SNARE proteins: potential regulators of melanosome movement. J Invest Dermatol. 2001;116:296-304 pubmed
  51. Matsumoto M, Miki T, Shibasaki T, Kawaguchi M, Shinozaki H, Nio J, et al. Noc2 is essential in normal regulation of exocytosis in endocrine and exocrine cells. Proc Natl Acad Sci U S A. 2004;101:8313-8 pubmed
    ..Thus, Noc2, a critical effector of Rab3, is essential in normal regulation of exocytosis in both endocrine and exocrine cells. ..
  52. Madison D, Krueger W, Cheng D, Trapp B, Pfeiffer S. SNARE complex proteins, including the cognate pair VAMP-2 and syntaxin-4, are expressed in cultured oligodendrocytes. J Neurochem. 1999;72:988-98 pubmed
    ..We discuss the potential involvement of SNARE complex proteins in a plasma membrane-directed transport mechanism targeting nascent myelin vesicles to the forming myelin sheath. ..
  53. Horikawa H, Saisu H, Ishizuka T, Sekine Y, Tsugita A, Odani S, et al. A complex of rab3A, SNAP-25, VAMP/synaptobrevin-2 and syntaxins in brain presynaptic terminals. FEBS Lett. 1993;330:236-40 pubmed
    ..Our results suggest tight linkage between the components involved in neurotransmitter release. ..