rab3a gtp binding protein


Summary: The most abundant member of the RAB3 GTP-BINDING PROTEINS. It is involved in calcium-dependent EXOCYTOSIS and is localized to neurons and neuroendocrine cells. This enzyme was formerly listed as EC

Top Publications

  1. Foletti D, Blitzer J, Scheller R. Physiological modulation of rabphilin phosphorylation. J Neurosci. 2001;21:5473-83 pubmed
  2. Park J, Kim J, Lee J, Kim J, Seo J, Kim A. GTP binds to Rab3A in a complex with Ca2+/calmodulin. Biochem J. 2002;362:651-7 pubmed
    ..Taken together, these results suggest that CaM may have a role in stimulating GTP binding to Rab3A that is complexed with GDI, which leads to the formation of an active GTP-bound form of the Rab3A-Ca(2+)/CaM complex. ..
  3. Yunes R, Michaut M, Tomes C, Mayorga L. Rab3A triggers the acrosome reaction in permeabilized human spermatozoa. Biol Reprod. 2000;62:1084-9 pubmed
  4. Yunes R, Tomes C, Michaut M, De Blas G, Rodriguez F, Regazzi R, et al. Rab3A and calmodulin regulate acrosomal exocytosis by mechanisms that do not require a direct interaction. FEBS Lett. 2002;525:126-30 pubmed
    ..Our results indicate that the inhibitory and stimulatory effects of Rab3A in different exocytic processes are mediated by different effectors. ..
  5. Yi Z, Yokota H, Torii S, Aoki T, Hosaka M, Zhao S, et al. The Rab27a/granuphilin complex regulates the exocytosis of insulin-containing dense-core granules. Mol Cell Biol. 2002;22:1858-67 pubmed
  6. Schoch S, Castillo P, Jo T, Mukherjee K, Geppert M, Wang Y, et al. RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature. 2002;415:321-6 pubmed
    ..These data indicate that RIM1alpha has a central function in integrating active zone proteins and synaptic vesicles into a molecular scaffold that controls neurotransmitter release. ..
  7. Leenders A, Lopes da Silva F, Ghijsen W, Verhage M. Rab3a is involved in transport of synaptic vesicles to the active zone in mouse brain nerve terminals. Mol Biol Cell. 2001;12:3095-102 pubmed
    ..These data indicate that rab3A has a function upstream of vesicle fusion in the activity-dependent transport of synaptic vesicles to and their docking at the active zone. ..
  8. Sze C, Bi H, Kleinschmidt DeMasters B, Filley C, Martin L. Selective regional loss of exocytotic presynaptic vesicle proteins in Alzheimer's disease brains. J Neurol Sci. 2000;175:81-90 pubmed
    ..These results suggest that there are selective and early defects in presynaptic vesicle proteins, but not synaptic plasma membrane proteins in AD and that defects correlate with cognitive dysfunction in this disease. ..
  9. Schlüter O, Basu J, Sudhof T, Rosenmund C. Rab3 superprimes synaptic vesicles for release: implications for short-term synaptic plasticity. J Neurosci. 2006;26:1239-46 pubmed

More Information


  1. Michaut M, Tomes C, De Blas G, Yunes R, Mayorga L. Calcium-triggered acrosomal exocytosis in human spermatozoa requires the coordinated activation of Rab3A and N-ethylmaleimide-sensitive factor. Proc Natl Acad Sci U S A. 2000;97:9996-10001 pubmed
    ..This process is suggested to be an essential part of the molecular mechanism of membrane fusion leading to the release of the acrosomal contents. ..
  2. Star E, Newton A, Murthy V. Real-time imaging of Rab3a and Rab5a reveals differential roles in presynaptic function. J Physiol. 2005;569:103-17 pubmed
    ..We propose that while Rab3a preferentially associates with recycling synaptic vesicles and modulates their trafficking, Rab5a is largely excluded from recycling vesicles. ..
  3. Thiagarajan R, Tewolde T, Li Y, Becker P, Rich M, Engisch K. Rab3A negatively regulates activity-dependent modulation of exocytosis in bovine adrenal chromaffin cells. J Physiol. 2004;555:439-57 pubmed
    ..Our results suggest that Rab3A in the GTP bound conformation prevents activity-dependent facilitation. ..
  4. Yaekura K, Julyan R, Wicksteed B, Hays L, Alarcon C, Sommers S, et al. Insulin secretory deficiency and glucose intolerance in Rab3A null mice. J Biol Chem. 2003;278:9715-21 pubmed
    ..Also, this study indicates, for the first time, that the in vivo insulin secretory dysfunction found in type-2 diabetes can lie solely at the level of defective insulin exocytosis. ..
  5. Tsuboi T, Fukuda M. Rab3A and Rab27A cooperatively regulate the docking step of dense-core vesicle exocytosis in PC12 cells. J Cell Sci. 2006;119:2196-203 pubmed
    ..Our findings indicate that Rab3A and Rab27A cooperatively regulate docking step(s) of dense-core vesicles to the plasma membrane. ..
  6. Tomes C, De Blas G, Michaut M, Farré E, Cherhitin O, Visconti P, et al. alpha-SNAP and NSF are required in a priming step during the human sperm acrosome reaction. Mol Hum Reprod. 2005;11:43-51 pubmed
    ..These results suggest a key role for alpha-SNAP/NSF in the AR, and strengthen our understanding of the molecular players involved in the vesicle-to-plasma membrane fusion taking place during exocytosis...
  7. Kajio H, Olszewski S, Rosner P, Donelan M, Geoghegan K, Rhodes C. A low-affinity Ca2+-dependent association of calmodulin with the Rab3A effector domain inversely correlates with insulin exocytosis. Diabetes. 2001;50:2029-39 pubmed
  8. Huang Y, Zakharenko S, Schoch S, Kaeser P, Janz R, Sudhof T, et al. Genetic evidence for a protein-kinase-A-mediated presynaptic component in NMDA-receptor-dependent forms of long-term synaptic potentiation. Proc Natl Acad Sci U S A. 2005;102:9365-70 pubmed
    ..Thus Rab3A and its effectors are general modules for four distinct types of PKA-dependent LTP in the brain. ..
  9. Tomes C, Roggero C, De Blas G, Saling P, Mayorga L. Requirement of protein tyrosine kinase and phosphatase activities for human sperm exocytosis. Dev Biol. 2004;265:399-415 pubmed
    ..Our results show that both tyrosine kinases and phosphatases play a central role in sperm exocytosis. ..
  10. Park J, Lee J, Kim J. Dissociation of RalA from synaptic membranes by Ca2+/calmodulin. Biochem Biophys Res Commun. 1999;263:765-9 pubmed
    ..Therefore, we examined if Ca2+/CaM can also cause the RalA to dissociate from SV membranes. In this study, we identified that Ca2+/CaM dissociates RalA as well as Rab3A from synaptic vesicles. ..
  11. Khanna R, Li Q, Sun L, Collins T, Stanley E. N type Ca2+ channels and RIM scaffold protein covary at the presynaptic transmitter release face but are components of independent protein complexes. Neuroscience. 2006;140:1201-8 pubmed
    ..These findings indicate that although the vesicle fusion and the vesicle docking mechanisms coexist at the transmitter release face they are not parts of a common stable complex. ..
  12. Miyauchi N, Saito A, Karasawa T, Harita Y, Suzuki K, Koike H, et al. Synaptic vesicle protein 2B is expressed in podocyte, and its expression is altered in proteinuric glomeruli. J Am Soc Nephrol. 2006;17:2748-59 pubmed
    ..These results suggest that SV2B is a functional molecule of podocyte, and SV2B may play a role in the expression and proper localization of CD2AP. ..
  13. Domoki F, Kis B, Gaspar T, Snipes J, Parks J, Bari F, et al. Rosuvastatin induces delayed preconditioning against oxygen-glucose deprivation in cultured cortical neurons. Am J Physiol Cell Physiol. 2009;296:C97-105 pubmed publisher
    ..Reduced neuronal ATP levels and ROS production after OGD may be directly involved in the mechanism of neuroprotection. ..
  14. Blundell J, Kaeser P, Sudhof T, Powell C. RIM1alpha and interacting proteins involved in presynaptic plasticity mediate prepulse inhibition and additional behaviors linked to schizophrenia. J Neurosci. 2010;30:5326-33 pubmed publisher
  15. Ward C, Faundes D, Foster J. The monomeric GTP binding protein, rab3a, is associated with the acrosome in mouse sperm. Mol Reprod Dev. 1999;53:413-21 pubmed
    ..These data identify the presence of rab3a in acrosomal membranes of mouse sperm and suggest that rab3a plays a role in the regulation of zona pellucida -induced acrosomal exocytosis. ..
  16. Yasuda T, Shibasaki T, Minami K, Takahashi H, Mizoguchi A, Uriu Y, et al. Rim2alpha determines docking and priming states in insulin granule exocytosis. Cell Metab. 2010;12:117-29 pubmed publisher
  17. Paulmann N, Grohmann M, Voigt J, Bert B, Vowinckel J, Bader M, et al. Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation. PLoS Biol. 2009;7:e1000229 pubmed publisher
  18. Davidsson P, Bogdanovic N, Lannfelt L, Blennow K. Reduced expression of amyloid precursor protein, presenilin-1 and rab3a in cortical brain regions in Alzheimer's disease. Dement Geriatr Cogn Disord. 2001;12:243-50 pubmed
    ..Due to the similarity of the expression of APP, PS-1 and rab3a, it is tempting to speculate whether there is a functional relationship between these proteins. ..
  19. Liu Y, Ren H, Wu C, Bai S, Zhang X, Ru B. Attenuation of zinc-induced neuronal death by the interaction of growth inhibitory factor with Rab3A in rat hippocampal neurons. Neurosci Lett. 2004;358:149-52 pubmed
    ..This result was supported by both Annexin -V FITC/propidium dual staining and chromosomal DNA analysis. These findings suggest that GIF may inhibit Zn(2+)-induced neuronal death via its interaction with Rab3A. ..
  20. Fukuda M. Alternative splicing in the first alpha-helical region of the Rab-binding domain of Rim regulates Rab3A binding activity: is Rim a Rab3 effector protein during evolution?. Genes Cells. 2004;9:831-42 pubmed
    ..Based on these findings, I propose that the Rab3A-effector function of Rim during secretory vesicle exocytosis is limited to the short form of the mammalian Rim RBD alone. ..
  21. Coleman W, Bill C, Bykhovskaia M. Rab3a deletion reduces vesicle docking and transmitter release at the mouse diaphragm synapse. Neuroscience. 2007;148:1-6 pubmed
    ..This result is consistent with the proposed role of rab3a in trafficking and targeting vesicles to the active zones...
  22. Piiper A, Leser J, Lutz M, Beil M, Zeuzem S. Subcellular distribution and function of Rab3A-D in pancreatic acinar AR42J cells. Biochem Biophys Res Commun. 2001;287:746-51 pubmed
    ..In conclusion, our data indicate that the different Rab3 proteins show distinct subcellular distribution, suggesting different impact on exocrine secretory response in dexamethasone-differentiated AR42J cells. ..
  23. Kapfhamer D, Valladares O, Sun Y, Nolan P, Rux J, Arnold S, et al. Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse. Nat Genet. 2002;32:290-5 pubmed
    ..Phenotypic assessment of earlybird mice and a null allele of Rab3a revealed anomalies in circadian period and sleep homeostasis, providing evidence that Rab3a-mediated synaptic transmission is involved in these behaviors. ..
  24. Gogolla N, Galimberti I, Deguchi Y, Caroni P. Wnt signaling mediates experience-related regulation of synapse numbers and mossy fiber connectivities in the adult hippocampus. Neuron. 2009;62:510-25 pubmed publisher
    ..Therefore, behavioral experience specifically regulates adult global stratum lucidum synapse numbers and hippocampal network structure through Wnt signaling. ..
  25. Manzur A, Sosa M, Seltzer A. Transient increase in rab 3A and synaptobrevin immunoreactivity after mild hypoxia in neonatal rats. Cell Mol Neurobiol. 2001;21:39-52 pubmed
    ..The transient nature of this effect possibly indicates the activation of endogenous neuroprotective mechanisms. ..
  26. Powell C, Schoch S, Monteggia L, Barrot M, Matos M, Feldmann N, et al. The presynaptic active zone protein RIM1alpha is critical for normal learning and memory. Neuron. 2004;42:143-53 pubmed
  27. Sakane A, Miyoshi J, Takai Y, Sasaki T. Analysis on the emerging role of Rab3 GTPase-activating protein in Warburg Micro and Martsolf syndrome. Methods Enzymol. 2008;438:131-9 pubmed publisher
    ..Here, we describe the procedures for the measurement of the GTP-bound pool of Rab3A with pull-down assay using mouse brains and the biochemical method for the measurement of glutamate release from mouse synaptosomes. ..
  28. Wu X, Rao K, Zhang H, Wang F, Sellers J, Matesic L, et al. Identification of an organelle receptor for myosin-Va. Nat Cell Biol. 2002;4:271-8 pubmed
  29. Smith R, Klein P, Koc Schmitz Y, Waldvogel H, Faull R, Brundin P, et al. Loss of SNAP-25 and rabphilin 3a in sensory-motor cortex in Huntington's disease. J Neurochem. 2007;103:115-23 pubmed
    ..SNAP 25 and rabphilin 3a are crucial for neurotransmitter release. Therefore, we suggest that a deficient pre-synaptic transmitter release may underlie some of the symptoms of HD. ..
  30. Silinsky E. Selective disruption of the mammalian secretory apparatus enhances or eliminates calcium current modulation in nerve endings. Proc Natl Acad Sci U S A. 2008;105:6427-32 pubmed publisher
    ..In contrast, cleavage of the synaptic vesicle SNARE (synaptobrevin) in conjunction with deletion of the vesicle-docking protein Rab3A greatly enhances the efficacy of calcium current modulation. ..
  31. Karpushev A, Levchenko V, Pavlov T, Lam V, Vinnakota K, Vandewalle A, et al. Regulation of ENaC expression at the cell surface by Rab11. Biochem Biophys Res Commun. 2008;377:521-525 pubmed publisher
    ..We conclude that ENaC channels, present on the apical plasma membrane, are being exchanged with channels from the intracellular pool in a Rab11-dependent manner. ..
  32. Fenster S, Chung W, Zhai R, Cases Langhoff C, Voss B, Garner A, et al. Piccolo, a presynaptic zinc finger protein structurally related to bassoon. Neuron. 2000;25:203-14 pubmed
    ..These data suggest that Piccolo plays a role in the trafficking of synaptic vesicles (SVs) at the active zone. ..
  33. Jöns T, Lehnardt S, Bigalke H, Heim H, Ahnert Hilger G. SNARE proteins and rab3A contribute to canalicular formation in parietal cells. Eur J Cell Biol. 1999;78:779-86 pubmed
    ..These data may provide evidence that SNARE proteins and rab3A are functionally involved in the stimulation-induced translocation of the H+/K(+)-ATPase. ..
  34. Richmond J, Broadie K. The synaptic vesicle cycle: exocytosis and endocytosis in Drosophila and C. elegans. Curr Opin Neurobiol. 2002;12:499-507 pubmed
    ..In neuromodulation, dcaps mutants provide the first genetic insight into possible roles of the CAPS protein in mediating dense core vesicle fusion and modulating synaptic vesicle fusion. ..
  35. Knipp M, Meloni G, Roschitzki B, Vasak M. Zn7metallothionein-3 and the synaptic vesicle cycle: interaction of metallothionein-3 with the small GTPase Rab3A. Biochemistry. 2005;44:3159-65 pubmed
    ..GDP. The interaction of Zn(7)MT-3 with Rab3A indicates that Zn(7)MT-3 is not merely a cellular Zn(2+) buffer, but actively participates in synaptic vesicle trafficking upstream of vesicle fusion. ..
  36. von Kriegstein K, Schmitz F. The expression pattern and assembly profile of synaptic membrane proteins in ribbon synapses of the developing mouse retina. Cell Tissue Res. 2003;311:159-73 pubmed publisher
    ..We conclude that ribbon synapse formation is a multistep process in which the concerted recruitment of synaptic membrane proteins is a relatively early event and clearly not the final step...
  37. Lin C, Huang C, Lin K, Cheng K, Yang D, Tsai Y, et al. Visualization of Rab3A dissociation during exocytosis: a study by total internal reflection microscopy. J Cell Physiol. 2007;211:316-26 pubmed
    ..The results provide direct evidence to support the hypothesis that GTP hydrolysis and rabphilin are involved in Rab3A dissociation from the vesicles and the occurrence of exocytosis. ..
  38. Sun L, Bittner M, Holz R. Rab3a binding and secretion-enhancing domains in Rim1 are separate and unique. Studies in adrenal chromaffin cells. J Biol Chem. 2001;276:12911-7 pubmed
  39. 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. ..
  40. Gevrey J, Laurent S, Saurin J, Nemoz Gaillard E, Regazzi R, Chevrier A, et al. Rab3a controls exocytosis in cholecystokinin-secreting cells. FEBS Lett. 2001;503:19-24 pubmed
    ..These results indicate that endocrine cell lines of intestinal origin express rab3A and rab3D proteins, but the GTP-bound form of rab3A only acts as a negative modulator in the control of cholecystokinin secretion from STC-1 cells. ..
  41. 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. ..
  42. de Siqueira K, de Lima F, Lima F, Taki M, da Cunha C, de Lima Reis S, et al. miR-124a expression contributes to the monophasic pattern of insulin secretion in islets from pregnant rats submitted to a low-protein diet. Eur J Nutr. 2018;57:1471-1483 pubmed publisher
    ..2 underexpression and from the changes in exocytotic elements that are influenced either directly or indirectly by miR-124a. ..
  43. De Blas G, Michaut M, Trevino C, Tomes C, Yunes R, Darszon A, et al. The intraacrosomal calcium pool plays a direct role in acrosomal exocytosis. J Biol Chem. 2002;277:49326-31 pubmed
    ..Our results show that a calcium efflux from the acrosome through IP(3)-sensitive channels is necessary downstream Rab3A activation during the membrane fusion process leading to acrosomal exocytosis. ..
  44. Liu R, Hannenhalli S, Bucan M. Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons. Genome Biol. 2009;10:R72 pubmed publisher
    ..This work introduces an integrative strategy of comparative genomics, experimental, and computational approaches to reveal aspects of a regulatory network controlling neuronal-specific expression of genes in presynaptic neurons. ..
  45. Baron R, Seabra M. Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate. Biochem J. 2008;415:67-75 pubmed publisher
    ..This effect is regulated by GGPP, which promotes the dissociation of RGGT and REP-Rab-GG to allow delivery of prenylated Rabs to membranes. ..
  46. Blennow K, Bogdanovic N, Heilig M, Grenfeldt B, Karlsson I, Davidsson P. Reduction of the synaptic protein rab3a in the thalamus and connecting brain regions in post-mortem schizophrenic brains. J Neural Transm (Vienna). 2000;107:1085-97 pubmed
  47. Dong S, Mulders W, Rodger J, Robertson D. Changes in neuronal activity and gene expression in guinea-pig auditory brainstem after unilateral partial hearing loss. Neuroscience. 2009;159:1164-74 pubmed publisher
    ..These results suggest that a decrease in inhibitory neurotransmission and an increase in membrane excitability may contribute to elevated neuronal spontaneous activity in the auditory brainstem following unilateral partial hearing loss. ..
  48. Davidsson P, Gottfries J, Bogdanovic N, Ekman R, Karlsson I, Gottfries C, et al. The synaptic-vesicle-specific proteins rab3a and synaptophysin are reduced in thalamus and related cortical brain regions in schizophrenic brains. Schizophr Res. 1999;40:23-9 pubmed
    ..05); and no differences in temporal cortex or cerebellum in schizophrenics compared with controls. Reduced synaptic density may be a prominent feature of the molecular neuropathology of schizophrenia. ..
  49. Foletti D, Scheller R. Developmental regulation and specific brain distribution of phosphorabphilin. J Neurosci. 2001;21:5461-72 pubmed
    ..We propose that the phosphorylation of rabphilin regulates neuronal activity through development and in a synapse-specific manner. ..
  50. Wong F, Stanley E. Rab3a interacting molecule (RIM) and the tethering of pre-synaptic transmitter release site-associated CaV2.2 calcium channels. J Neurochem. 2010;112:463-73 pubmed publisher
    ..The differing results might be reconciled, however, in a model where a RIM family member contributes to a protein bridge that anchors the pre-fusion secretory vesicle to the calcium channel protein complex. ..
  51. Betz A, Thakur P, Junge H, Ashery U, Rhee J, Scheuss V, et al. Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron. 2001;30:183-96 pubmed
    ..The Munc13-1/RIM1 interaction may create a functional link between synaptic vesicle tethering and priming, or it may regulate the priming reaction itself, thereby determining the number of fusion-competent vesicles. ..
  52. Pavlos N, Gr Nborg M, Riedel D, Chua J, Boyken J, Kloepper T, et al. Quantitative analysis of synaptic vesicle Rabs uncovers distinct yet overlapping roles for Rab3a and Rab27b in Ca2+-triggered exocytosis. J Neurosci. 2010;30:13441-53 pubmed publisher
    ..Finally, we demonstrate that selective modulation of the GTP/GDP switch mechanism of Rab27b impairs SV recycling, suggesting that Rab27b, probably in concert with Rab3s, is involved in SV exocytosis...
  53. Predic J, Soskic V, Bradley D, Godovac Zimmermann J. Monitoring of gene expression by functional proteomics: response of human lung fibroblast cells to stimulation by endothelin-1. Biochemistry. 2002;41:1070-8 pubmed
    ..We propose that the functional proteomic methods are competitive with and have some advantages compared to expression profiling methods for monitoring gene expression. ..