Affinage

RAB3A

Ras-related protein Rab-3A · UniProt P20336

Length
220 aa
Mass
25.0 kDa
Annotated
2026-06-10
100 papers in source corpus 66 papers cited in narrative 66 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB3A is a small GTPase that regulates the late, Ca2+-triggered steps of regulated exocytosis at synaptic vesicles and secretory granules (PMID:7911226, PMID:9194562, PMID:12510060). It is targeted to vesicle membranes distal to the Golgi and attaches via geranylgeranylation of both cysteines in its C-terminal Cys-X-Cys motif; this prenylation is necessary and sufficient for membrane binding and for interaction with Rab GDI, while correct vesicle targeting is independent of the lipid modification (PMID:1648935, PMID:1315770, PMID:7991565). RAB3A cycles between a cytosolic GDP-bound state and a membrane-associated GTP-bound state, an ordered cycle controlled by the GEF GRAB, by a specific Rab3A-GAP and the TBC-domain GAP FLJ13130, and by GDI, which antagonizes the exchange factor but not GAP activity (PMID:8226729, PMID:11516400, PMID:19077034). GTP-bound RAB3A engages a set of effectors through its effector domain and a unique RabCDR pocket resolved crystallographically: rabphilin-3A, RIM1/RIM2, Munc13-1 (recruited via RIM), and Myosin-Va, coupling vesicles to the active zone, priming, and transport machinery (PMID:8384302, PMID:10025402, PMID:12578829, PMID:16704978, PMID:21349835). Functionally, RAB3A is not essential for basal transmission but sets the Ca2+ sensitivity of fusion, mediates activity-dependent recruitment and docking of vesicles to the active zone, and is required for mossy-fiber LTP, with GTP hydrolysis coupled to the exocytotic event itself (PMID:7929154, PMID:9194562, PMID:9252190, PMID:11598194, PMID:17637832). Beyond neurons, RAB3A controls dense-core and insulin granule docking and first-phase insulin release, acrosomal exocytosis in sperm, and a Rab3A/Slp4-a/NMHC IIA complex that positions lysosomes peripherally for plasma-membrane repair (PMID:12510060, PMID:10727281, PMID:16684812, PMID:27325790). Disease-linked perturbations of this cycle—mutant huntingtin sequestering RAB3A from Rab3-GAP1 to impair BDNF secretion—underscore its role in regulated release (PMID:27559163).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1991 High

    Established how RAB3A attaches to vesicle membranes, defining the lipid basis of its membrane cycle and separating targeting from modification.

    Evidence Compactin inhibition, mevalonate rescue, C-terminal Cys-X-Cys mutagenesis, and in vitro geranylgeranylation with mass-spectrometric mapping of both cysteines

    PMID:1315770 PMID:1648935 PMID:7991565

    Open questions at the time
    • Does not define which vesicle membrane protein or determinant directs pre-prenylation targeting
    • Structural basis of GDI recognition of the prenyl group not resolved here
  2. 1992 High

    Defined RAB3A as a regulated GTP/GDP switch with dedicated, isoform-specific GAP, exchange, and GDI activities acting in an ordered cycle, distinguishing its regulation from Ras.

    Evidence In vitro GTPase, nucleotide exchange and GDI assays on processed vs unmodified protein, effector-domain mutagenesis, and Ras-analogous mutant analysis in PC12 cells

    PMID:1331063 PMID:1847129 PMID:8226729 PMID:8387493

    Open questions at the time
    • Molecular identity of the physiologic GEF and GAP not yet established at this stage
    • How nucleotide state is coupled to membrane association in vivo unresolved
  3. 1993 High

    Identified rabphilin-3A as the first GTP-dependent RAB3A effector and dissected its bipartite architecture, linking RAB3A to a Ca2+/phospholipid-sensing module.

    Evidence Cross-linking purification, cDNA cloning, GTPgammaS- vs GDP-dependent binding, and domain-fragment binding/GTPase assays

    PMID:1597436 PMID:8226731 PMID:8262955 PMID:8384302

    Open questions at the time
    • Does not establish how the effector translates RAB3A activation into membrane fusion
    • In vivo requirement for the interaction not yet tested
  4. 1994 High

    Demonstrated genetically that RAB3A is dispensable for basal exocytosis but required for vesicle recruitment during repetitive activity, and that it recruits rabphilin-3A to synapses.

    Evidence Rab3A knockout mice with CA1 electrophysiology, synaptic protein immunoblotting, and rabphilin localization analysis

    PMID:7911226 PMID:7946335

    Open questions at the time
    • Compensation by other Rab3 isoforms (B/C) confounds null phenotype interpretation
    • Step at which RAB3A acts (docking vs priming vs fusion) not yet resolved
  5. 1994 High

    Linked GTP hydrolysis by RAB3A directly to the exocytotic event, defining the membrane-release arm of the cycle.

    Evidence GDP/GTP ratio measurements in synaptosomal fractions with alpha-latrotoxin-evoked massive exocytosis

    PMID:7929154

    Open questions at the time
    • Whether hydrolysis is cause or consequence of fusion not distinguished
    • GAP responsible for stimulus-coupled hydrolysis not identified here
  6. 1997 High

    Refined the functional step to a late docking/fusion event downstream of priming, and showed RAB3A tunes the Ca2+ sensitivity of release and mossy-fiber LTP.

    Evidence Electrophysiological dissection (RRP, release kinetics, mfLTP, PPF) in Rab3A-null mice plus glutamate-release assays with forskolin

    PMID:9194562 PMID:9252190 PMID:9856469

    Open questions at the time
    • Molecular effectors mediating the Ca2+-sensitivity effect not yet defined
    • Mechanism of presynaptic LTP expression downstream of RAB3A unresolved
  7. 1999 High

    Provided the atomic structure of activated RAB3A bound to rabphilin-3A, defining the effector-specificity determinant (RabCDR pocket).

    Evidence 2.6 Å X-ray crystallography of Rab3A/GTP/Mg2+–rabphilin-3A effector domain with biochemical binding validation

    PMID:10025402

    Open questions at the time
    • Structures with other effectors (RIM, Myosin-Va) not solved
    • Does not address conformational coupling to membrane release
  8. 2001 High

    Identified the physiologic GEF GRAB and showed RAB3A is required for activity-dependent recruitment and docking of vesicles to the active zone.

    Evidence GRAB cloning with in vitro GEF assay and secretion readouts, plus EM of vesicle distribution in Rab3A-null synaptosomes

    PMID:11516400 PMID:11598194

    Open questions at the time
    • How GRAB is spatially activated at release sites not defined
    • RIM/Munc13 contribution to the recruitment phenotype not yet integrated
  9. 2003 High

    Extended RAB3A function to endocrine secretion, establishing it acts downstream of Ca2+ at the granule exocytosis step and is required for first-phase insulin release.

    Evidence Glucose tolerance, isolated islet secretion, glucose oxidation and Ca2+ imaging in Rab3A-null mice; systematic RIM2 binding specificity mapping

    PMID:12510060 PMID:12578829

    Open questions at the time
    • Effector mediating the insulin-secretion defect not pinpointed
    • Relative roles of Rab3 paralogs in beta-cells not resolved
  10. 2007 High

    Demonstrated that RAB3A promotes vesicle docking through obligatory GTP/GDP cycling acting upstream of Munc18-1, and quantified its docking role at the NMJ.

    Evidence Chromaffin-cell expression of GTP- and GDP-locked mutants with EM in Munc18-1 null cells, and EM/electrophysiology in Rab3A-null NMJ

    PMID:16684812 PMID:17637832 PMID:17640821

    Open questions at the time
    • Biochemical linkage between RAB3A cycling and Munc18-1 not fully defined
    • Cooperative mechanism with Rab27A at docking sites unresolved
  11. 2011 High

    Positioned RAB3A within the RIM/Munc13-1 priming pathway and identified Myosin-Va as a GTP-dependent partner for vesicle transport.

    Evidence Epistasis with RIM-binding-deficient Munc13-1 and Munc18-1 co-expression in capacitance assays; GST pull-down, AUC, and motility assays for Myosin-Va

    PMID:16704978 PMID:21349835 PMID:21689256

    Open questions at the time
    • Order of effector engagement during a single fusion cycle not resolved
    • How Myosin-Va transport connects to active-zone docking unclear
  12. 2016 High

    Revealed a non-neuronal RAB3A role in lysosome positioning and plasma-membrane repair, and a disease mechanism in which mutant huntingtin disrupts RAB3A cycling.

    Evidence siRNA Rab screen with lysosome positioning, PM repair and co-IP defining a Rab3A/Slp4-a/NMHC IIA complex; co-IP, GTP pull-down and rescue in HD knock-in mice/astrocytes

    PMID:27325790 PMID:27559163

    Open questions at the time
    • Whether the same effector logic operates at synapses and lysosomes not tested
    • How huntingtin physically blocks Rab3-GAP1 access structurally undefined
  13. 2023 Medium

    Showed post-translational control of the RAB3A cycle through regulator modification, with O-GlcNAcylation of RAB3A and palmitoylation of Rab3gap1 reshaping GTP loading and exocytosis.

    Evidence PTM detection with GTP-binding/activity assays in HCC cells and xenografts; zDHHC9 manipulation with Rab3A-GTP and ANP secretion assays in cardiomyocytes

    PMID:30237463 PMID:37325411

    Open questions at the time
    • O-GlcNAcylation site on RAB3A and its enzymes not mapped
    • Generality of GAP spatial segregation across secretory cell types untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the RAB3A nucleotide cycle is temporally and spatially coordinated with the SNARE fusion machinery to convert effector engagement into a single Ca2+-triggered fusion event remains unresolved.
  • No reconstituted fusion system couples RAB3A cycling to SNARE-mediated fusion
  • Quantitative timing of GEF/GAP action relative to Ca2+ influx not defined
  • Effector hand-off sequence (rabphilin/RIM/Munc13/Myosin-Va) during a fusion cycle unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 5 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0031410 cytoplasmic vesicle 4 GO:0005829 cytosol 3 GO:0005886 plasma membrane 3 GO:0005764 lysosome 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1474165 Reproduction 3 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3
Partners
CALM1GRABMYO5ARAB3GAP1RIM1RIM2RPH3ASYN1
Complex memberships
Rab3A/Slp4-a/NMHC IIA lysosome-positioning complex

Evidence

Reading pass · 66 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Rab3A associates with chromaffin granule membranes in adrenal medulla cells; ~30% is cytosolic and ~70% particulate, with membrane association requiring hydrophobic modification (not extractable by salt but solubilized by detergent or urea), suggesting interaction with an intrinsic membrane protein or fatty acid acylation. Subcellular fractionation, immunoadsorption, antibody against dopamine β-hydroxylase, detergent/salt extraction Proceedings of the National Academy of Sciences of the United States of America Medium 2165599
1991 Rab3A is attached to synaptic vesicle membranes via a carboxy-terminal Cys-X-Cys sequence that undergoes polyisoprenylation (geranylgeranylation); this modification is required for membrane association and is inhibited by compactin in a mevalonate-dependent manner. Correct intracellular targeting to synaptic vesicles is independent of the lipid modification, suggesting targeting and modification are consecutive events. Compactin inhibition, mevalonate rescue, biochemical fractionation, mutation of C-terminal Cys-X-Cys, expression in nonneuronal cells Neuron High 1648935
1991 Rab3A colocalizes with synaptic vesicle markers at the cell periphery but is absent from the Golgi area, indicating it associates with vesicles distally to the Golgi. Massive exocytosis causes translocation of Rab3A to the cell surface, demonstrating that Rab3A undergoes a membrane-association/dissociation cycle linked to exocytosis. Immunofluorescence, developmental/functional stage analysis in neurons and neuroendocrine cells, frog motor end-plate exocytosis experiments The Journal of cell biology Medium 1655810
1991 A Rab3A-specific GTPase-activating protein (GAP) exists in rat brain, distributed between cytosolic and membrane fractions; a distinct membrane-associated factor also accelerates Rab3A GTPase activity. Ras-specific GAP has no effect on Rab3A, establishing specificity. In vitro GTPase activity assays, subcellular fractionation, heat/trypsin sensitivity, gel filtration The Journal of biological chemistry Medium 1847129
1991 Rab3A protein is concentrated at the active zone of the rat neuromuscular junction, suggesting a role in synaptic vesicle attachment and fusion at this specialized membrane domain. Immunoperoxidase ultrastructural localization (immunoelectron microscopy) Biochemical and biophysical research communications Medium 1324664
1992 Synthetic peptides corresponding to the Rab3A effector domain stimulate complete exocytotic degranulation in mast cells in a Mg2+- and ATP-dependent manner, suggesting that sustained GTP-Rab3A activation causes exocytotic membrane fusion via competition with endogenous Rab3 for a target effector. Patch-clamp capacitance measurements, intracellular perfusion with synthetic peptides in mast cells Nature Medium 1331813
1992 The geranylgeranyl moiety (but not the carboxyl methyl group) of Rab3A is essential and sufficient for membrane binding and for interaction with Rab GDI (GDP dissociation inhibitor). Bacterially expressed unmodified Rab3A lacks both activities, which are restored by geranylgeranylation alone. In vitro geranylgeranylation of recombinant protein, membrane binding assay, GDI sensitivity assay The Journal of biological chemistry High 1315770
1992 Rab3A effector domain peptide (rab3AL) stimulates amylase release from permeabilized pancreatic acini in an ATP-dependent manner at sub-stimulatory Ca2+ concentrations and potentiates GTPγS-induced secretion; a Rab2 effector domain peptide is inactive, indicating specificity. Streptolysin-O permeabilized acini secretion assay, competitive peptide inhibition Proceedings of the National Academy of Sciences of the United States of America Medium 1371881
1992 Rab3A effector domain mutations (residues 51–59) abolish sensitivity to Rab3A-GRF (guanine nucleotide releasing factor) and decrease affinity for GRF, while only one mutation in this region abolishes GAP sensitivity, indicating that GRF and GAP interact with overlapping but distinct determinants in the effector domain. C-terminal truncation of 34 residues has no effect on GAP sensitivity but facilitates GRF stimulation. Site-directed mutagenesis, in vitro GTPase and nucleotide exchange assays The Journal of biological chemistry High 1331063
1992 In PC12 cells, cytosolic Rab3A is predominantly GDP-bound while membrane-associated Rab3A is ~50% GTP-bound. GDI and GRF act only on GDP-Rab3A and require post-translational modification; GAP does not preferentially act on processed Rab3A and acts on GTP-Rab3A. GDI antagonizes GRF but not GAP activity, establishing an ordered GTP/GDP cycling mechanism. Nucleotide binding assays, GDI/GRF/GAP activity assays, subcellular fractionation of PC12 cells The Journal of biological chemistry High 8226729
1992 A putative Rab3A target protein of ~85–86 kDa (smg p25A target, later identified as rabphilin-3A) was purified from bovine brain membranes by cross-linking with GTPγS-bound Rab3A; the GDP-bound form of Rab3A and other small GTPases (Ras, RhoA, Rab11) do not cross-link to this target, establishing GTP-dependent and isoform-specific interaction. Chemical cross-linking (disuccinimidyl suberate), SDS-PAGE, protein purification, competitive inhibition The Journal of biological chemistry Medium 1597436
1993 Rabphilin-3A was cloned and shown to interact selectively with the GTPγS-bound (active) form of Rab3A but not the GDP-bound form, both with purified bovine brain protein and recombinant rabphilin-3A; the protein contains two C2 domains homologous to synaptotagmin and protein kinase C. cDNA cloning, expression in COS7 cells, co-immunoprecipitation/pull-down with GTPγS- vs GDP-Rab3A, immunoblot Molecular and cellular biology High 8384302
1993 Rabphilin-3A has two functionally distinct domains: the N-terminal domain (aa 1–280) binds GTPγS-Rab3A but not phospholipid/Ca2+, while the C-terminal domain (aa 281–704 containing C2 domains) binds phospholipid in a Ca2+-dependent manner but does not bind Rab3A. In vitro binding assays with recombinant domain fragments, 45Ca2+ binding, phospholipid binding The Journal of biological chemistry High 8262955
1993 Rabphilin-3A (N-terminal domain) inhibits Rab3A-GAP-stimulated GTPase activity while only weakly stimulating basal GTPase activity, suggesting rabphilin-3A maintains Rab3A in the GTP-bound active state by blocking GAP access. In vitro GTPase assay with purified Rab3A-GAP, full-length and domain fragments of rabphilin-3A The Journal of biological chemistry Medium 8226731
1993 Point mutations in the Rab3A effector domain (residues 51–59) abolish cross-linking of Rab3A to a ~85 kDa brain membrane target protein and also reduce binding to GDI, GRF, and GAP, indicating the effector domain mediates multiple protein interactions. Preloading with GTPγS enhanced cross-linking, confirming GTP-dependence. Site-directed mutagenesis, chemical cross-linking, competitive inhibition assays The Journal of biological chemistry Medium 8226995
1993 Rab3A mutants analogous to oncogenic Ras: Q81L and S31V reduce basal GTPase activity but, unlike Ras mutants, remain sensitive to Rab3A-GAP; N135I has >100-fold increased GDP dissociation rate; A166V has modestly increased GDP dissociation. Q81L and wild-type Rab3A have similar GTP-bound fractions in vivo, indicating that Rab3A regulation differs fundamentally from Ras. Site-directed mutagenesis, in vitro GTPase assay, nucleotide binding/dissociation kinetics, GAP/GRF sensitivity assays The Journal of biological chemistry High 8387493
1994 Rab geranylgeranyltransferase/Rab escort protein catalyzes geranylgeranylation of both C-terminal adjacent cysteines in Rab3A (XCXC motif), confirmed by direct structural analysis of tryptic peptides via HPLC and electrospray mass spectrometry. In vitro prenylation with [3H]geranylgeranyl pyrophosphate, tryptic digest, HPLC, electrospray mass spectrometry Proceedings of the National Academy of Sciences of the United States of America High 7991565
1994 Synaptic vesicle-bound Rab3A is almost exclusively GTP-bound, whereas cytosolic Rab3A contains only GDP. Stimulation with α-latrotoxin (causing massive exocytosis) produces a significant increase in the GDP/GTP ratio of Rab3A, indicating that GTP hydrolysis by Rab3A is coupled to synaptic vesicle exocytosis. Nucleotide analysis (GDP/GTP ratio) in synaptosomal fractions, α-latrotoxin stimulation, subcellular fractionation The Journal of biological chemistry High 7929154
1994 Overexpression of wild-type Rab3A and the Q81L (hydrolysis-deficient) mutant inhibits Ca2+-dependent exocytosis in chromaffin cells; a constitutively GTP-bound form (Q81L) also inhibits Ca2+-dependent secretion from permeabilized cells, indicating Rab3A acts as a negative regulator or part of a pre-fusion complex. Transient transfection with human growth hormone reporter, flow cytometry, Ca2+-dependent secretion from permeabilized cells The Journal of biological chemistry Medium 8144603
1994 Rab3A is expressed in the synaptic vesicle protein cycle as a late-stage associate: it undergoes fast anterograde axonal transport but not retrograde transport, suggesting Rab3A associates with synaptic vesicle precursors in the soma and is degraded rather than recycled within nerve terminals. Sciatic nerve ligation, quantitative immunocytochemistry, immunoblotting, immunogold electron microscopy European journal of cell biology Medium 8521869
1994 Rab3A effector domain peptides specifically stimulate insulin exocytosis in electroporated beta-cells; cross-linking identified a cytosolic protein doublet (REEP-1 and REEP-2) that specifically binds the Rab3A effector domain and is released from membranes upon stimulation of exocytosis. Electroporation of insulin-secreting cells, 125I-labeled photoactivatable cross-linking peptide, competitive inhibition The Journal of biological chemistry Medium 7961732
1994 Rab3A-deficient mice show normal basic synaptic transmission but significantly increased synaptic depression during short trains of repetitive stimuli (15–30 stimuli at 14 Hz). Rabphilin protein levels are decreased 70% in these mice. Rab3A is not essential for exocytosis but plays a role in vesicle recruitment during repetitive stimulation. Homologous recombination knockout, electrophysiology (CA1 pyramidal cells), immunoblotting for >20 synaptic proteins Nature High 7911226
1994 Synaptic targeting of rabphilin-3A to nerve terminals depends on Rab3A/3C: in neurons primarily expressing Rab3A, rabphilin-3A is decreased in synapses and accumulates in perikarya of Rab3A-deficient mice; neurons expressing Rab3C maintain normal synaptic rabphilin levels. Rabphilin-3A binds Rab3C in vitro, suggesting Rab3A/C recruit rabphilin-3A to synaptic vesicle membranes. Rab3A knockout mouse analysis, immunofluorescence, in vitro binding assay with Rab3C Neuron High 7946335
1994 Rabphilin-3A Rab3A-binding domain (N-terminal ~170 aa including Cys-rich region coordinating two Zn2+ ions) is necessary for Rab3A interaction; C2 domains are required for efficient membrane attachment in PC12 cells. A Rab3A mutant (T54A) that does not bind rabphilin in vitro still co-localizes with GFP-rabphilin, indicating Rab3A targeting is independent of rabphilin interaction. Mutagenesis, GFP-rabphilin fusion localization, zinc binding assay, in vitro binding Molecular and cellular biology Medium 8756657
1994 Rabphilin-3A is phosphorylated by cAMP-dependent protein kinase (PKA) at its N-terminal region (~0.8 mol phosphate/mol protein); Rab3A itself is not a PKA substrate, identifying rabphilin-3A as a downstream effector regulated by cAMP/PKA signaling. In vitro kinase assay with purified PKA and recombinant proteins, 32P incorporation Biochemical and biophysical research communications Medium 7945346
1995 Rabin3 (a novel 50 kDa protein) interacts with Rab3A and Rab3D but not Rab3C, Rab2, Ran, or Ras; interaction requires the Rab3A effector domain (mutations F51L, V55E, G56D abolish interaction; V52A increases it). Rabin3 possesses no detectable GAP or GEF activity and overexpression does not affect secretion. Yeast two-hybrid, GST pull-down, nucleotide exchange/GTPase assays, overexpression in chromaffin cells Molecular and cellular biology Medium 7532276
1995 Rabphilin-3A is associated with synaptic vesicles through a vesicle membrane protein independent of Rab3A: removal of endogenous Rab3A by RabGDI or addition of excess exogenous Rab3A does not affect rabphilin-3A binding to vesicles; trypsin treatment of vesicles abolishes rabphilin-3A binding. Salt extraction, RabGDI treatment, exogenous protein binding assay, trypsin digestion, saturation binding The Journal of biological chemistry Medium 7806490
1995 Rabphilin-3A overexpression enhances stimulated secretion (~30%) in chromaffin cells; antisense inhibition reduces secretion (~30%); C2 domain deletion mutants strongly inhibit exocytosis in intact and permeabilized cells. This identifies rabphilin-3A as a positive regulator of exocytosis downstream of Rab3A-GTP. cDNA transfection in chromaffin cells, growth hormone secretion reporter, antisense inhibition, permeabilized cell Ca2+-dependent secretion assay The Journal of biological chemistry Medium 7622481
1996 Rab3A and Rab3B both target to large dense-core vesicles in PC12 cells and bind rabphilin-3A in a GTP-dependent manner. Overexpression of Rab3A modestly inhibits Ca2+-evoked NE release, whereas Rab3B and Rab3B N135I stimulate secretion efficiency and increase NE accumulation in LDCVs without affecting vesicle number or docking, demonstrating functional non-redundancy despite similar targeting. Stable transfection, immunofluorescence, membrane fractionation, [3H]NE secretion assay, rabphilin-3A binding assay The Journal of biological chemistry Medium 8636125
1997 Rab3A-deficient mice show normal readily releasable pool size but altered Ca2+-triggered fusion: more exocytic events occur within a brief time after nerve impulse arrival, indicating Rab3A acts specifically at a late step in synaptic vesicle docking/fusion after the priming step. Electrophysiological analysis (quantal content, readily releasable pool, kinetics of release) in Rab3A-null mice Nature High 9194562
1997 Mossy fiber LTP in hippocampal CA3 is abolished in Rab3A-deficient mice, while short-term plasticities are normal, demonstrating that Rab3A is required for a specific form of presynaptically expressed LTP. Genetic knockout, electrophysiology (mossy fiber LTP, PPF, frequency facilitation) Nature High 9252190
1997 Ca2+/calmodulin causes Rab3A to dissociate from synaptic membranes in vitro, forming a 1:1 complex requiring both the lipidated C terminus and bound guanine nucleotide. A peptide corresponding to Rab3A residues 62–85 prevents this dissociation and disrupts calmodulin-Rab3A complexes; calmodulin's effect differs from GDI in being Ca2+-dependent and less stringent regarding nucleotide state. In vitro membrane dissociation assay, peptide competition, complex formation analysis The Journal of biological chemistry Medium 9252412
1997 Antisense depletion of Rab3A in chromaffin cells increases secretory activity at low Ca2+ concentrations (0.2–4 µM) without changing maximal activity at 10 µM Ca2+, and increases secretion after a train of depolarizing stimuli, indicating Rab3A participates in setting the Ca2+ sensitivity of exocytosis. Antisense oligonucleotide microinjection, patch-clamp capacitance measurements, Ca2+ dialysis Journal of neurochemistry Medium 9721737
1998 In mossy fiber synapses, cAMP/forskolin enhances glutamate release by multiple mechanisms; only the direct activation of the secretory apparatus (as monitored by ionomycin-induced Ca2+-dependent release) requires Rab3A, establishing that Rab3A acts at the level of Ca2+ sensitivity of the fusion machinery in mfLTP. Synaptosomal glutamate release assay (KCl, sucrose, ionomycin), Rab3A-deficient mice, forskolin treatment Neuron High 9856469
1999 Crystal structure of activated Rab3A/GTP/Mg2+ bound to the effector domain of rabphilin-3A resolved to 2.6 Å: Rab3A contacts rabphilin-3A at two distinct interfaces—switch I/II regions (nucleotide-sensitive) and a deep 'RabCDR' pocket unique to Rab3A that interacts with a SGAWFF structural element of rabphilin-3A. The RabCDR is proposed as a determinant of effector specificity. X-ray crystallography (2.6 Å), biochemical binding validation Cell High 10025402
1999 Rab3A is associated with the acrosomal membrane of rat sperm; a synthetic Rab3 effector domain peptide inhibits Ca2+ ionophore-induced acrosomal exocytosis in a concentration-dependent manner, suggesting Rab3A acts as a regulatory component (possibly inhibitory) in the acrosome reaction. RT-PCR, immunoblot, immunofluorescence, immunogold EM, acrosome reaction assay with effector domain peptide Developmental biology Medium 10373312
2000 GTP-bound recombinant Rab3A triggers acrosomal exocytosis in permeabilized human spermatozoa; GDP-loaded Rab3A and GTP-loaded Rab11 are inactive; recombinant GDI inhibits GTPγS-stimulated acrosome reaction. This establishes that Rab3A (or another Rab3 isoform) is directly required for acrosomal exocytosis. Streptolysin-O permeabilization, recombinant Rab3A (GTP vs GDP form), GDI inhibition, acrosome reaction assay Biology of reproduction High 10727281
2000 Ca2+-triggered acrosomal exocytosis requires active NSF; Rab3A (GTP form) protects NSF from NEM inhibition and blocks exchange with dominant-negative NSF mutants; Rab3A activation requires active NSF. This defines a Rab3A–NSF interaction in which GTP-Rab3A formation and NSF activity are mutually dependent during membrane fusion. Permeabilized sperm exocytosis assay, NEM treatment, dominant-negative NSF mutants, functional reconstitution Proceedings of the National Academy of Sciences of the United States of America Medium 10954749
2001 GRAB (guanine nucleotide exchange factor for Rab3A) is a physiologic GEF for Rab3A; it interacts with both InsP6K1 and Rab3A; overexpression/manipulation of GRAB regulates depolarization-induced dopamine release from PC12 cells and nicotinic agonist-induced hGH release from chromaffin cells. Protein cloning, co-IP, in vitro GEF assay, depolarization-induced secretion assay Neuron High 11516400
2001 Rab3A deletion abolishes activity-dependent recruitment of synaptic vesicles to the active zone: in normal mice, Ca2+-dependent depolarization causes vesicle accumulation near/at the active zone; this accumulation is completely absent in Rab3A-null mice without affecting total vesicle number. Post-stimulation replenishment of docked vesicles is also impaired. Electron microscopy of synaptosomes, vesicle distribution analysis, secretion recovery assays in Rab3A-null mice Molecular biology of the cell High 11598194
2001 Rim1 Rab3A-binding and secretion-enhancing domains are structurally separate: a ~30-aa sequence N-terminal to the zinc finger is the minimal Rab3A-GTP binding domain of Rim1, entirely distinct from the zinc finger alone which promotes secretion; Rim1 does not alter Ca2+ sensitivity of secretion but increases the rate of ATP-dependent priming. Domain deletion/truncation mutants, Rab3A-GTP binding assay, permeabilized chromaffin cell secretion assay The Journal of biological chemistry Medium 11278839
2003 Rabconnectin-3 (alpha/beta heterodimer) associates with Rab3-GEP on synaptic vesicles: rabconnectin-3β (1490 aa with 7 WD domains) directly binds Rab3 GEP while rabconnectin-3α does not; Rab3 GAP binding by the complex is indirect. This positions rabconnectin-3 as a scaffold regulating Rab3A GTP/GDP cycling on synaptic vesicles. Co-immunoprecipitation from synaptic vesicle fractions, direct binding assay, cDNA cloning Genes to cells Medium 12786944
2003 Rim1, Rim2, rabphilin, and Noc2 show distinct Rab binding specificities: Rim2 binds Rab3A/B/C/D and Rab8A; acidic cluster residues E50, E51, E52 in Rim2's α1 region are critical determinants for Rab3A recognition (identified by mutagenesis and chimeric analysis). Co-transfection binding assay with 42 Rab proteins, site-directed mutagenesis, chimeric protein analysis The Journal of biological chemistry High 12578829
2003 Rab3A-null mice develop fasting hyperglycemia and absent first-phase insulin release with normal glucose oxidation and Ca2+ flux in beta-cells, placing Rab3A function downstream of Ca2+ signaling at the level of secretory granule transport/exocytosis; isolated islets from Rab3A-/- mice show ~60–70% reduction in secretagogue-induced insulin release. Genetic knockout, glucose tolerance test, arginine stimulation, isolated islet secretion, glucose oxidation, Ca2+ imaging The Journal of biological chemistry High 12510060
2004 Synapsin I stimulates GTP binding and GTPase activity of Rab3A on synaptic vesicles; conversely, Rab3A inhibits synapsin I binding to F-actin and synapsin-induced actin bundling and vesicle clustering. Synapsin prevents RabGDI-induced Rab3A dissociation from vesicles; Rab3A levels on synaptic vesicles are decreased in synapsin knockout mice. In vitro GTPase assay, F-actin binding/bundling assay, vesicle clustering assay, RabGDI competition, synapsin knockout mice analysis The Journal of biological chemistry High 15265868
2005 Zn7-metallothionein-3 (Zn7MT-3) binds reversibly to GDP-Rab3A (KD = 2.6 µM) but not to GTP-Rab3A; the binding site maps to the effector-binding region of Rab3A. GDP exchange kinetics are unaffected, suggesting Zn7MT-3 binds without blocking nucleotide exchange. Affinity precipitation, surface plasmon resonance, mutagenesis Biochemistry Medium 15736926
2006 Rab3A and Rab27A cooperatively regulate the docking of dense-core vesicles to the plasma membrane in PC12 cells: siRNA silencing of either reduces docked vesicle number without altering fusion kinetics; simultaneous silencing produces a greater reduction than either alone. siRNA knockdown, TIRF microscopy of single PC12 cells, vesicle docking quantification Journal of cell science High 16684812
2006 Munc13-1 and ubMunc13-2 active zone recruitment depends on binding to RIM1α, which is a Rab3A-interacting molecule. A point mutation I121N in Munc13-1/ubMunc13-2 abolishes RIM1α binding in vitro; RIM1α-binding-deficient ubMunc13-2(I121N) is not efficiently recruited to synapses; Munc13 levels are decreased at mossy fiber active zones in RIM1α-null mice. Pull-down assays, yeast two-hybrid, immunostaining of RIM1α-null mice, confocal microscopy The Journal of biological chemistry High 16704978
2007 Rab3A is rapidly exchanged between secretory granules and cytosol (fast FRAP recovery), whereas Rab27A persists on granule membranes after stimulation. Both Rab3A and Rab27A are preferentially recruited to newly synthesized (immature) secretory granules ~20 minutes after release from the trans-Golgi network. FRAP of EGFP-Rab3A and ECFP-Rab27A in PC12 cells, live-cell imaging, colocalization with secretogranin II Journal of cell science Medium 17311845
2007 Rab3A promotes vesicle docking in chromaffin cells in a manner requiring GTP/GDP cycling: both GTP-locked and GDP-locked Rab3A mutants fail to promote docking. Furthermore, wild-type Rab3A does not promote docking in munc18-1 null cells, and both locked mutants decrease docked vesicles in that background, establishing that Rab3A-dependent docking requires nucleotide cycling and acts upstream of Munc18-1. Chromaffin cell expression of Rab3A mutants, electron microscopy vesicle distribution, Munc18-1 null cells PloS one High 17637832
2007 Rab3A deletion reduces vesicle docking at the NMJ by 26%, reduces evoked quantal content by 27%, and reduces spontaneous mini frequency by 28%, with the greatest effect at low Ca2+ (>50% reduction at 0.2–0.5 mM Ca2+), without altering Ca2+ cooperativity but reducing Ca2+ sensitivity of release. Rab3A-null mice, electron microscopy of NMJ, focal electrophysiology, Ca2+ manipulation Neuroscience High 17640821
2008 A TBC domain protein FLJ13130 (novel TBC-domain Rab3A-GAP) promotes GTPase activity of Rab3A in vitro and reduces GTP-Rab3A levels in living cells in a catalytic-residue-dependent manner (R134K mutant inactive); it also acts on Rab22A, Rab27A, and Rab35, indicating broad but specific Rab-GAP activity near the plasma membrane. Cell-based GTP-Rab3A assay, in vitro GAP assay, catalytic mutant analysis, dense-core vesicle localization screen Genes to cells Medium 19077034
2009 APP anterograde transport vesicles contain Rab3A and kinesin-1C; assembly of kinesin-1C with APP in this vesicle type requires Rab3A GTPase activity. APP is also cleaved by alpha-secretase (ADAM10) within these Rab3A-positive transport vesicles. Time-lapse microscopy, immunoisolation of vesicles, GTPase-activity-deficient Rab3A mutants The Journal of neuroscience Medium 19923287
2009 cAMP/Epac activates Rab3A (GDP→GTP exchange) in human sperm downstream of soluble adenylyl cyclase; this activation is required for acrosomal exocytosis. Recombinant Epac does not directly exchange GDP on Rab3A in vitro, indicating indirect Rab3A-GEF activation. Rab3A functions downstream of Epac but independently of Rap1. Rab3A-GTP pull-down assay, Epac-selective cAMP analog, permeabilized sperm exocytosis, in vitro GEF assay The Journal of biological chemistry Medium 19546222
2010 Rab3A readily dissociates from synaptic vesicle membranes during Ca2+-triggered exocytosis and is susceptible to Rab-GDI-mediated membrane extraction; it resides on distinct but overlapping synaptic vesicle pools compared to Rab27b. iTRAQ quantitative mass spectrometry, immunoblotting, immunofluorescence, stimulation experiments, GDI extraction assay The Journal of neuroscience High 20926670
2011 Rab3A involvement in vesicle priming is mediated via RIM/Munc13-1: in cells overexpressing a RIM-binding-deficient Munc13-1 mutant (128-Munc13-1), the effect of Rab3A on PMA-induced secretion is abolished; Munc18-1 promotes Rab3A dissociation from vesicles and acts downstream of Munc13-1/RIM/Rab3A; co-expression of Munc18-1 reverses the secretory block caused by GTP-locked Rab3A (Q81L). Overexpression of Rab3A mutants, siRNA knockdown, capacitance measurements, PMA stimulation Traffic Medium 21689256
2011 Myosin-Va tail directly interacts with GTP-bound (but not nucleotide-free) Rab3A; interaction confirmed by GST pull-down from rat brain synaptosomes, co-immunofluorescence in primary neurons, and sedimentation velocity analytical ultracentrifugation with recombinant proteins. This interaction is proposed to mediate synaptic vesicle transport. GST affinity chromatography, co-immunofluorescence, sedimentation velocity analytical ultracentrifugation, squid axoplasm in vitro motility assay The Journal of biological chemistry High 21349835
2012 Rab3A GTPase cycle governs ribbon binding and dissociation at photoreceptor ribbon synapses: GDP analogs and a GTPase-deficient Rab3A mutant block dissociation; the GTPase-deficient mutant blocks synaptic release in an activity-dependent, frequency-dependent manner by interfering with vesicle resupply to release sites. Fluorescently labeled Rab3A delivered via patch pipette into rods/cones, non-hydrolyzable GDP analogs, GTPase-deficient mutant, paired pre/postsynaptic recordings The Journal of neuroscience High 22593061
2013 Membrane-bound GTP-Rab3A stabilizes α-synuclein on synaptic vesicle membranes; the RabGDI-Hsp90 complex that controls Rab3A membrane dissociation also regulates α-synuclein dissociation. A GTPase-deficient Rab3A mutant, dominant-negative GDI, and Hsp90 inhibitors all increase α-synuclein membrane sequestration. Density gradient sedimentation, co-immunoprecipitation, GTPase-deficient Rab3A mutant, Hsp90 inhibitors (radicicol/geldanamycin), α-synuclein binding assay The Journal of biological chemistry Medium 23344955
2013 β-Adrenergic receptor (βAR) activation via cAMP/Epac increases the Rab3A–RIM1α interaction and redistributes synaptic vesicles closer to the presynaptic membrane, enhancing glutamate release in a PLC-dependent manner; Epac also translocates Munc13-1 to the particulate fraction. Co-immunoprecipitation, subcellular fractionation, glutamate release assay, βAR agonist (isoproterenol), Epac-selective analog, calphostin C, immunoelectron microscopy The Journal of biological chemistry Medium 24036110
2015 Active ARF6 increases GDP→GTP exchange on Rab3A during acrosomal exocytosis in human sperm; this is part of an ARF6 signaling cascade (via phospholipase D, PI(4,5)P2, PLC, and inositol 1,4,5-trisphosphate-dependent Ca2+ release) required for acrosome exocytosis. GDP/GTP exchange pull-down assay, permeabilized sperm exocytosis, pharmacological inhibitors, active ARF6 addition The Journal of biological chemistry Medium 25713146
2016 Rab3A forms a complex with synaptotagmin-like protein 4a (Slp4-a) and nonmuscle myosin heavy chain IIA (NMHC IIA) to position lysosomes at the cell periphery; silencing Rab3A or either effector collapses lysosomes to the perinuclear region and inhibits plasma membrane repair after SLO-mediated damage. Systematic siRNA screen of Rab family, lysosome positioning assay, plasma membrane repair assay, co-immunoprecipitation The Journal of cell biology High 27325790
2016 Mutant huntingtin associates with Rab3A and prevents GTP-Rab3A from binding Rab3-GAP1, disrupting GTP→GDP conversion on Rab3A and impairing BDNF vesicle docking and secretion from HD astrocytes; overexpression of Rab3A rescues impaired BDNF vesicle docking and secretion. Co-immunoprecipitation, Rab3A-GTP pull-down, vesicle docking assay, BDNF secretion assay, HD140Q knock-in mice, Rab3A overexpression rescue The Journal of neuroscience High 27559163
2018 O-GlcNAcylation of Rab3A attenuates its GTP-binding activity, inhibiting its function; this modification has opposite effects on HCC metastasis and mitochondrial oxidative phosphorylation compared to unmodified Rab3A, indicating O-GlcNAcylation modulates Rab3A activity in HCC cells. O-GlcNAc detection assays, GTP-binding activity assays, overexpression/knockdown in HCC cells, in vivo xenograft assay Cell death & disease Medium 30237463
2021 Rab11 interacts with GRAB (GEF for Rab3A) and with Rab3A itself; Rab11-positive vesicles transiently interact with lysosomes at the cell periphery as part of the mechanism for lysosome exocytosis. Silencing exocyst subunit Sec15 (a Rab11 effector) impairs lysosome exocytosis, suggesting a Rab11→Rab3A cascade. siRNA knockdown, co-immunoprecipitation, live-cell imaging, lysosome exocytosis assay Journal of cell science Medium 34100549
2023 Palmitoylation of Rab3gap1 by the S-acyltransferase zDHHC9 spatially segregates Rab3gap1 from Rab3A, elevating Rab3A-GTP levels, forming Rab3A-positive peripheral vesicles, and impairing exocytosis that limits atrial natriuretic peptide (ANP) release from cardiomyocytes. zDHHC9 manipulation, Rab3A-GTP measurement, vesicle formation assay, ANP secretion assay in cardiomyocytes JACC. Basic to translational science Medium 37325411

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 The role of Rab3A in neurotransmitter release. Nature 428 7911226
1993 Rabphilin-3A, a putative target protein for smg p25A/rab3A p25 small GTP-binding protein related to synaptotagmin. Molecular and cellular biology 378 8384302
1997 The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion. Nature 361 9194562
1999 Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A. Cell 299 10025402
1997 Rab3A is essential for mossy fibre long-term potentiation in the hippocampus. Nature 297 9252190
1991 Association of Rab3A with synaptic vesicles at late stages of the secretory pathway. The Journal of cell biology 227 1655810
1994 Evidence for the involvement of Rab3A in Ca(2+)-dependent exocytosis from adrenal chromaffin cells. The Journal of biological chemistry 210 8144603
1990 Association of the GTP-binding protein Rab3A with bovine adrenal chromaffin granules. Proceedings of the National Academy of Sciences of the United States of America 209 2165599
1994 Synaptic targeting of rabphilin-3A, a synaptic vesicle Ca2+/phospholipid-binding protein, depends on rab3A/3C. Neuron 183 7946335
1992 Exocytotic fusion is activated by Rab3a peptides. Nature 167 1331813
2006 Rab3A and Rab27A cooperatively regulate the docking step of dense-core vesicle exocytosis in PC12 cells. Journal of cell science 160 16684812
2003 Distinct Rab binding specificity of Rim1, Rim2, rabphilin, and Noc2. Identification of a critical determinant of Rab3A/Rab27A recognition by Rim2. The Journal of biological chemistry 159 12578829
1993 Two functionally different domains of rabphilin-3A, Rab3A p25/smg p25A-binding and phospholipid- and Ca(2+)-binding domains. The Journal of biological chemistry 136 8262955
1994 Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A. Proceedings of the National Academy of Sciences of the United States of America 135 7991565
1992 A synthetic peptide of the rab3a effector domain stimulates amylase release from permeabilized pancreatic acini. Proceedings of the National Academy of Sciences of the United States of America 133 1371881
1995 Evidence that the Rab3a-binding protein, rabphilin3a, enhances regulated secretion. Studies in adrenal chromaffin cells. The Journal of biological chemistry 128 7622481
2003 Insulin secretory deficiency and glucose intolerance in Rab3A null mice. The Journal of biological chemistry 110 12510060
1992 A possible target protein for smg-25A/rab3A small GTP-binding protein. The Journal of biological chemistry 106 1597436
1998 Mechanism of action of rab3A in mossy fiber LTP. Neuron 105 9856469
2009 APP anterograde transport requires Rab3A GTPase activity for assembly of the transport vesicle. The Journal of neuroscience : the official journal of the Society for Neuroscience 102 19923287
1996 Rab3A small GTP-binding protein in Ca(2+)-dependent exocytosis. Genes to cells : devoted to molecular & cellular mechanisms 100 9078389
1991 rab3A attachment to the synaptic vesicle membrane mediated by a conserved polyisoprenylated carboxy-terminal sequence. Neuron 97 1648935
2016 A Rab3a-dependent complex essential for lysosome positioning and plasma membrane repair. The Journal of cell biology 90 27325790
2001 Rab3a is involved in transport of synaptic vesicles to the active zone in mouse brain nerve terminals. Molecular biology of the cell 90 11598194
1999 Subcellular distribution and function of Rab3A, B, C, and D isoforms in insulin-secreting cells. Molecular endocrinology (Baltimore, Md.) 90 9973251
2013 α-Synuclein membrane association is regulated by the Rab3a recycling machinery and presynaptic activity. The Journal of biological chemistry 87 23344955
1993 Mutants of Rab3A analogous to oncogenic Ras mutants. Sensitivity to Rab3A-GTPase activating protein and Rab3A-guanine nucleotide releasing factor. The Journal of biological chemistry 87 8387493
2016 Mutant Huntingtin Impairs BDNF Release from Astrocytes by Disrupting Conversion of Rab3a-GTP into Rab3a-GDP. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 27559163
2010 Quantitative analysis of synaptic vesicle Rabs uncovers distinct yet overlapping roles for Rab3a and Rab27b in Ca2+-triggered exocytosis. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 20926670
2001 GRAB: a physiologic guanine nucleotide exchange factor for Rab3A, which interacts with inositol hexakisphosphate kinase. Neuron 85 11516400
2009 Epac activates the small G proteins Rap1 and Rab3A to achieve exocytosis. The Journal of biological chemistry 84 19546222
2006 Binding to Rab3A-interacting molecule RIM regulates the presynaptic recruitment of Munc13-1 and ubMunc13-2. The Journal of biological chemistry 84 16704978
2000 Calcium-triggered acrosomal exocytosis in human spermatozoa requires the coordinated activation of Rab3A and N-ethylmaleimide-sensitive factor. Proceedings of the National Academy of Sciences of the United States of America 82 10954749
2000 Rab3A triggers the acrosome reaction in permeabilized human spermatozoa. Biology of reproduction 81 10727281
1992 The geranylgeranyl moiety but not the methyl moiety of the smg-25A/rab3A protein is essential for the interactions with membrane and its inhibitory GDP/GTP exchange protein. The Journal of biological chemistry 80 1315770
1991 Regulation of the GTPase activity of the ras-like protein p25rab3A. Evidence for a rab3A-specific GAP. The Journal of biological chemistry 77 1847129
1992 Amino acid residues in the Ras-like GTPase Rab3A that specify sensitivity to factors that regulate the GTP/GDP cycling of Rab3A. The Journal of biological chemistry 76 1331063
1999 Identification of Rab3A GTPase as an acrosome-associated small GTP-binding protein in rat sperm. Developmental biology 74 10373312
1996 Distinct functional properties of Rab3A and Rab3B in PC12 neuroendocrine cells. The Journal of biological chemistry 74 8636125
1995 Interaction cloning of Rabin3, a novel protein that associates with the Ras-like GTPase Rab3A. Molecular and cellular biology 71 7532276
1997 Ca2+/calmodulin causes Rab3A to dissociate from synaptic membranes. The Journal of biological chemistry 70 9252412
2002 Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse. Nature genetics 68 12244319
1995 Nonneuronal expression of Rab3A: induction during adipogenesis and association with different intracellular membranes than Rab3D. Proceedings of the National Academy of Sciences of the United States of America 63 7753798
1993 Rab3A GTPase-activating protein-inhibiting activity of Rabphilin-3A, a putative Rab3A target protein. The Journal of biological chemistry 63 8226731
1994 Rabphilin-3A is associated with synaptic vesicles through a vesicle protein in a manner independent of Rab3A. The Journal of biological chemistry 61 7806490
2001 Rab3A is required for brain-derived neurotrophic factor-induced synaptic plasticity: transcriptional analysis at the population and single-cell levels. The Journal of neuroscience : the official journal of the Society for Neuroscience 60 11517266
1995 The GTPase Rab3a is associated with large dense core vesicles in bovine chromaffin cells and rat PC12 cells. Journal of cell science 57 7615682
2007 Differential dynamics of Rab3A and Rab27A on secretory granules. Journal of cell science 56 17311845
2004 Synapsin is a novel Rab3 effector protein on small synaptic vesicles. II. Functional effects of the Rab3A-synapsin I interaction. The Journal of biological chemistry 56 15265868
1996 Role of the Rab3A-binding domain in targeting of rabphilin-3A to vesicle membranes of PC12 cells. Molecular and cellular biology 54 8756657
1994 GTP cleavage by the small GTP-binding protein Rab3A is associated with exocytosis of synaptic vesicles induced by alpha-latrotoxin. The Journal of biological chemistry 52 7929154
2003 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 to cells : devoted to molecular & cellular mechanisms 51 12786944
2005 Zn7metallothionein-3 and the synaptic vesicle cycle: interaction of metallothionein-3 with the small GTPase Rab3A. Biochemistry 48 15736926
2008 Identification and characterization of a novel Tre-2/Bub2/Cdc16 (TBC) protein that possesses Rab3A-GAP activity. Genes to cells : devoted to molecular & cellular mechanisms 47 19077034
2003 Glomerular podocytes possess the synaptic vesicle molecule Rab3A and its specific effector rabphilin-3a. The American journal of pathology 47 12937130
2009 The SNARE protein SNAP-29 interacts with the GTPase Rab3A: Implications for membrane trafficking in myelinating glia. Journal of neuroscience research 46 19170188
2004 Mice deficient for the synaptic vesicle protein Rab3a show impaired spatial reversal learning and increased explorative activity but none of the behavioral changes shown by mice deficient for the Rab3a regulator Gdi1. The European journal of neuroscience 46 15078563
2008 Loss of RAB-3/A in Caenorhabditis elegans and the mouse affects behavioral response to ethanol. Genes, brain, and behavior 44 18397381
2011 Glucagon-like peptide-1 enhances glucokinase activity in pancreatic β-cells through the association of Epac2 with Rim2 and Rab3A. Endocrinology 43 22147008
2016 Rab3a and Rab10 are regulators of lysosome exocytosis and plasma membrane repair. Small GTPases 42 27687479
2000 Rab3A and Rab3D control the total granule number and the fraction of granules docked at the plasma membrane in PC12 cells. Traffic (Copenhagen, Denmark) 42 11208087
2001 Rab3a and SNARE proteins: potential regulators of melanosome movement. The Journal of investigative dermatology 41 11180007
2013 β-Adrenergic receptors activate exchange protein directly activated by cAMP (Epac), translocate Munc13-1, and enhance the Rab3A-RIM1α interaction to potentiate glutamate release at cerebrocortical nerve terminals. The Journal of biological chemistry 40 24036110
2007 Rab3a deletion reduces vesicle docking and transmitter release at the mouse diaphragm synapse. Neuroscience 39 17640821
1999 The monomeric GTP binding protein, rab3a, is associated with the acrosome in mouse sperm. Molecular reproduction and development 38 10398417
1994 Rab3A effector domain peptides induce insulin exocytosis via a specific interaction with a cytosolic protein doublet. The Journal of biological chemistry 38 7961732
2021 Rab11 is required for lysosome exocytosis through the interaction with Rab3a, Sec15 and GRAB. Journal of cell science 37 34100549
2012 RIM, Munc13, and Rab3A interplay in acrosomal exocytosis. Experimental cell research 36 22248876
2005 Alpha-synuclein binding to rab3a in multiple system atrophy. Neuroscience letters 36 15854772
1993 The Rab3A GTPase interacts with multiple factors through the same effector domain. Mutational analysis of cross-linking of Rab3A to a putative target protein. The Journal of biological chemistry 36 8226995
2007 The role of Rab3a in secretory vesicle docking requires association/dissociation of guanidine phosphates and Munc18-1. PloS one 34 17637832
1993 Structure of the murine rab3A gene: correlation of genomic organization with antibody epitopes. The Biochemical journal 33 7687127
2014 Rab3a promotes brain tumor initiation and progression. Molecular biology reports 32 24965146
2000 Evidence of Rab3A expression, regulation of vesicle trafficking, and cellular secretion in response to heregulin in mammary epithelial cells. Molecular and cellular biology 31 11074007
1997 Rat basophilic leukaemia (RBL) cells overexpressing Rab3a have a reversible block in antigen-stimulated exocytosis. The Biochemical journal 31 9163319
2018 O-GlcNAcylation on Rab3A attenuates its effects on mitochondrial oxidative phosphorylation and metastasis in hepatocellular carcinoma. Cell death & disease 30 30237463
2015 ADP ribosylation factor 6 (ARF6) promotes acrosomal exocytosis by modulating lipid turnover and Rab3A activation. The Journal of biological chemistry 30 25713146
2001 Rab3a binding and secretion-enhancing domains in Rim1 are separate and unique. Studies in adrenal chromaffin cells. The Journal of biological chemistry 30 11278839
1995 Rab3a, a small GTP-binding protein, undergoes fast anterograde transport but not retrograde transport in neurons. European journal of cell biology 30 8521869
2021 Small Rab GTPases in Intracellular Vesicle Trafficking: The Case of Rab3A/Raphillin-3A Complex in the Kidney. International journal of molecular sciences 29 34299299
2011 Involvement of Rab3A in vesicle priming during exocytosis: interaction with Munc13-1 and Munc18-1. Traffic (Copenhagen, Denmark) 29 21689256
1993 Regulation of the GTPase cycle of the neuronally expressed Ras-like GTP-binding protein Rab3A. The Journal of biological chemistry 29 8226729
2011 Myosin5a tail associates directly with Rab3A-containing compartments in neurons. The Journal of biological chemistry 28 21349835
2007 Biochemical, molecular and behavioral phenotypes of Rab3A mutations in the mouse. Genes, brain, and behavior 28 16734774
2003 Rab3A negatively regulates activity-dependent modulation of exocytosis in bovine adrenal chromaffin cells. The Journal of physiology 28 14694148
1998 Regulation of the Ca2+ sensitivity of exocytosis by Rab3a. Journal of neurochemistry 28 9721737
1995 Double in situ hybridization reveals overlapping neuronal populations expressing the low molecular weight GTPases Rab3a and Rab3b in Rat brain. The European journal of neuroscience 28 7620619
1994 Phosphorylation of Rabphilin-3A, a putative target protein for Rab3A, by cyclic AMP-dependent protein kinase. Biochemical and biophysical research communications 28 7945346
2002 Rab3A and calmodulin regulate acrosomal exocytosis by mechanisms that do not require a direct interaction. FEBS letters 27 12163174
1992 Localization of smg p25A/rab3A p25, a small GTP-binding protein, at the active zone of the rat neuromuscular junction. Biochemical and biophysical research communications 27 1324664
2006 Distinct role of Rab3A and Rab3B in secretory activity of rat melanotrophs. American journal of physiology. Cell physiology 26 16822953
2001 Reduced expression of amyloid precursor protein, presenilin-1 and rab3a in cortical brain regions in Alzheimer's disease. Dementia and geriatric cognitive disorders 26 11351135
2000 Small Gtpase rab3A is associated with melanosomes in melanoma cells. Pigment cell research 26 11041209
2016 Rab3A, Rab27A, and Rab35 regulate different events during mouse oocyte meiotic maturation and activation. Histochemistry and cell biology 25 26791531
1997 Rab3A immunolocalization in the mammalian vestibular end-organs during development and comparison with synaptophysin expression. Brain research. Developmental brain research 24 9088571
1992 Localization of the ras-like rab3A protein in the adult rat brain. Brain research 24 1330210
2023 zDHHC9 Regulates Cardiomyocyte Rab3a Activity and Atrial Natriuretic Peptide Secretion Through Palmitoylation of Rab3gap1. JACC. Basic to translational science 23 37325411
2012 Rab3A mediates vesicle delivery at photoreceptor ribbon synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 22593061
2010 Cooperative regulation of neurotransmitter release by Rab3a and synapsin II. Molecular and cellular neurosciences 22 20338242
1994 Developmental changes in the localization of the synaptic vesicle protein rab3A in rat brain. Neuroscience 22 7830899

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