Affinage

VAMP3

Vesicle-associated membrane protein 3 · UniProt Q15836

Length
100 aa
Mass
11.3 kDa
Annotated
2026-06-11
59 papers in source corpus 38 papers cited in narrative 38 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

VAMP3 (cellubrevin) is an R-SNARE (v-SNARE) resident on recycling endosomes that drives membrane fusion across diverse secretory and trafficking pathways by forming ternary SNARE complexes with cognate t-SNAREs (PMID:12130530, PMID:17651732, PMID:21094665). In cell fusion assays VAMP3 partners productively with syntaxin1/SNAP-25, syntaxin1/SNAP-23, and syntaxin4/SNAP-25, but not syntaxin4/SNAP-23, and the N-terminal domain of syntaxin4 negatively regulates fusion (PMID:17651732); in cellular contexts it assembles with syntaxin 4/SNAP23 on Weibel-Palade bodies, with STX6 and STX6/VTI1B on recycling endosomes, and with SNAP23/syntaxin-2 in cytokine-secreting cells (PMID:21094665, PMID:22573826, PMID:27791468, PMID:24373201). Through these complexes VAMP3 mediates polarized exocytosis of recycling-endosome membrane to deliver cargo to the cell surface — β1- and α3β1-integrins, MT1-MMP and secreted MMP2/MMP9, the NKCC2 cotransporter, proteolipid protein, transferrin receptor, and transcytotic TfR vesicles across the blood-brain barrier — thereby supporting cell adhesion, migration, matrix degradation, invasion, and physiological electrolyte handling (PMID:19910495, PMID:19159614, PMID:22573826, PMID:27551042, PMID:21490207, PMID:40601634, PMID:21586284). It also serves as the fusion SNARE for regulated secretion in multiple cell types, including platelet alpha- and dense-granule release, mast cell degranulation, endothelial VWF secretion, astrocyte glutamate-transporter recycling and BDNF exocytosis, neuronal exosome release, and inflammatory cytokine (IL-6, TNFα) secretion from macrophages and dendritic cells that contributes to inflammatory pain (PMID:12130530, PMID:35990647, PMID:33224946, PMID:25864578, PMID:34707216, PMID:32195080, PMID:37965323, PMID:40977280). Within the autophagy/endosome system VAMP3 mediates MVB-autophagosome fusion (amphisome formation) and recycling-endosome fusion with bacteria-containing autophagic vacuoles during xenophagy (PMID:19781582, PMID:27791468). VAMP3 activity is positioned and tuned by upstream regulators: PI4K2A/PtdIns4P promotes its endosomal trafficking and Q-SNARE pairing (PMID:25002402), Rab8 drives its clustering at fusion sites (PMID:26034069), the chaperone WDFY2 sequesters it on endosomal tubules until phosphorylation releases it for polarized secretion (PMID:31253801, PMID:40977280), and Goliath/RNF167 and Hrd1 E3 ligases ubiquitylate it to control recycling and cargo surface delivery (PMID:23353890, PMID:32257542). Genetic knockout established that VAMP3 is dispensable for insulin-stimulated GLUT4 translocation, transferrin recycling, and bulk phagocytosis in vivo, defining its roles as selective rather than housekeeping (PMID:11238894, PMID:10888677).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1997 Medium

    Established the foundational hypothesis that VAMP3 acts as a v-SNARE pairing with syntaxin 4 to drive regulated vesicle delivery to the plasma membrane.

    Evidence Dominant-negative cytoplasmic domain expression and syntaxin 4 co-IP of GLUT4 vesicles in adipocytes

    PMID:9111311

    Open questions at the time
    • Did not distinguish VAMP3 from other VAMP isoforms functionally
    • Inferential for GLUT4 specifically; later challenged
  2. 2000 High

    Resolved the GLUT4 question by showing VAMP2, not VAMP3, is the essential v-SNARE for insulin-stimulated GLUT4 translocation, refining VAMP3's substrate selectivity.

    Evidence Tetanus-toxin cleavage with toxin-resistant SNARE rescue and GLUT4 translocation imaging in L6 myoblasts

    PMID:10888677

    Open questions at the time
    • Negative result for VAMP3 does not exclude partial/redundant roles
    • Cell-type specific (myoblasts)
  3. 2000 Medium

    Demonstrated VAMP3 delivers recycling-endosome membrane to nascent phagosomes, linking it to polarized focal exocytosis during membrane expansion.

    Evidence GFP/exofacial epitope tagging and live focal-exocytosis imaging in macrophages

    PMID:10791982

    Open questions at the time
    • Correlative localization; SNARE partners at the phagosome not defined
    • Functional requirement not genetically tested here
  4. 2001 High

    Genetic knockout defined VAMP3 as non-essential for bulk housekeeping trafficking, forcing the field toward specialized, redundancy-buffered roles.

    Evidence VAMP3-null mice with GLUT4, phagocytosis, pinocytosis, and transferrin recycling assays

    PMID:11238894

    Open questions at the time
    • Compensation by other VAMPs not excluded
    • Specialized secretory pathways not assayed
  5. 2002 High

    Identified VAMP3 as a required v-SNARE for regulated granule secretion, expanding its role beyond constitutive recycling into regulated exocytosis.

    Evidence Recombinant VAMP competition in permeabilized platelets, MS co-IP with syntaxin 4, and granule-release readouts

    PMID:12101283 PMID:12130530

    Open questions at the time
    • VAMP3 vs VAMP8 redundancy in platelets partially overlapping
    • Phagocytosis effect modest and particle-selective
  6. 2007 Medium

    Defined VAMP3's permissive and forbidden SNARE pairings biochemically, establishing the combinatorial rules for its fusion activity.

    Evidence Cell fusion assay with full-length SNAREs and syntaxin4 N-terminal deletion mutagenesis

    PMID:17651732

    Open questions at the time
    • No reconstituted liposome fusion or structural validation
    • syntaxin4/SNAP-23 result conflicts with in-cell complexes reported elsewhere
  7. 2009 Medium

    Placed VAMP3 at a specific autophagy step (MVB-autophagosome/amphisome fusion) distinct from the VAMP7-dependent lysosomal step, mapping its pathway position.

    Evidence siRNA knockdown with morphological and biochemical fusion analysis in K562 cells

    PMID:19781582

    Open questions at the time
    • t-SNARE partners at MVB-autophagosome interface not defined here
    • Single cell line
  8. 2009 High

    Connected VAMP3 to invasive cell behavior by showing it traffics MMPs and integrins to the surface to enable matrix degradation and migration.

    Evidence DN, RNAi, and tetanus toxin inhibition with secretion, surface-integrin, gelatin degradation, and invasion assays in fibrosarcoma cells

    PMID:19159614 PMID:19910495

    Open questions at the time
    • Direct SNARE partner for MMP/integrin carriers not fully resolved
    • In vivo tumor relevance not tested
  9. 2011 Medium

    Generalized VAMP3's recycling-endosome-to-surface delivery role across cell types (oligodendrocyte PLP, macrophage podosome dynamics), identifying syntaxin 4 as the prime acceptor Q-SNARE.

    Evidence siRNA/DN, VAMP3-deficient and mocha mutant mice, and migration/spreading assays

    PMID:21490207 PMID:21586284

    Open questions at the time
    • Quantitative contribution vs other delivery routes unclear
    • syntaxin4 assignment context-dependent
  10. 2012 Medium

    Identified VAMP3-STX6 as an endosomal SNARE pairing routing integrin through recycling endosomes and the TGN to the surface, refining the trafficking itinerary.

    Evidence Reciprocal Co-IP, siRNA, surface-delivery and chemotaxis assays

    PMID:22573826

    Open questions at the time
    • Single lab; STX6 vs syntaxin4 usage not reconciled mechanistically
  11. 2013 High

    Revealed ubiquitylation as a post-translational control of VAMP3 trafficking, showing E3 ligases gate its recycling-endosome function.

    Evidence Goliath/Godzilla/RNF167 ubiquitylation assays with VAMP3 lysine mutagenesis and endosome morphology in fly and mammalian cells

    PMID:23353890

    Open questions at the time
    • Deubiquitylase and physiological signals that trigger ubiquitylation not defined
    • Effect on SNARE complex assembly unresolved
  12. 2014 High

    Established a lipid- and kinase-dependent mechanism positioning VAMP3 on endosomes and licensing its Q-SNARE pairing.

    Evidence PI4K2A Co-IP/MS, siRNA, acute PtdIns4P depletion, and Vti1a association/transferrin recycling assays

    PMID:25002402

    Open questions at the time
    • How PtdIns4P physically recruits/orients VAMP3 not structurally defined
  13. 2015 Medium

    Identified Rab8 as the spatial regulator that clusters VAMP3 at fusion sites (immune synapse, cilium base), separating vesicle polarization from docking/fusion competence.

    Evidence Dominant-negative Rab8, TCR recycling, and co-localization across T cells and NIH-3T3 cells

    PMID:26034069

    Open questions at the time
    • Direct vs indirect Rab8-VAMP3 link not established
    • Effector bridging Rab8 to VAMP3 unknown
  14. 2015 High

    Extended VAMP3 to astrocyte physiology, showing Ca2+-independent cycling that controls surface glutamate transporters and endocytosed cargo recycling.

    Evidence VAMP2/VAMP3 KO mice, STED/TIRF single-vesicle imaging, and glutamate uptake assays

    PMID:25864578

    Open questions at the time
    • cAMP-to-VAMP3 signaling link mechanistically incomplete
  15. 2016 High

    Demonstrated in vivo physiological output of VAMP3 by linking it to constitutive NKCC2 apical delivery and blood-pressure regulation, and defined a STX6-VTI1B-VAMP3 xenophagy complex.

    Evidence VAMP3-NKCC2 Co-IP, in vivo TAL silencing and KO mice with blood pressure; ternary SNARE Co-IP and CRISPR KO in GAS xenophagy

    PMID:27551042 PMID:27791468

    Open questions at the time
    • Constitutive vs stimulated delivery branch point not molecularly resolved
    • RABGEF1-to-SNARE coupling detail limited
  16. 2017 High

    Broadened VAMP3's secretory repertoire to shear-induced endothelial microRNA secretion and to general constitutive secretion conserved with the Drosophila ortholog.

    Evidence siRNA with shear-stress and miRNA secretion assays plus mTORC1 inhibition; combinatorial RNAi secretion assays across species

    PMID:28403141 PMID:28716920

    Open questions at the time
    • Mechanism of non-vesicular miRNA export via VAMP3 incomplete
    • YKT6/VAMP3 functional relationship not dissected
  17. 2019 High

    Identified WDFY2 as an endosomal chaperone that sequesters VAMP3 to restrain invasive secretion, establishing a brake on VAMP3-dependent MT1-MMP delivery.

    Evidence WDFY2-VAMP3 Co-IP, CRISPR KO, VAMP3 redistribution imaging, and MT1-MMP secretion/ECM degradation/invasion assays

    PMID:31253801

    Open questions at the time
    • Trigger releasing VAMP3 from WDFY2 not defined here (later shown to be phosphorylation)
  18. 2020 Medium

    Linked VAMP3 to neuronal exosome release, endothelial VWF secretion/thrombosis, and Hrd1/H2S-controlled CD36 surface delivery, showing signal-dependent tuning of VAMP3 output.

    Evidence bFGF-driven MVB-PM fusion imaging and EV proteomics; shear-induced VWF secretion with in vivo thrombosis model; Hrd1 S-sulfhydration and VAMP3 ubiquitylation assays

    PMID:32195080 PMID:32257542 PMID:33224946

    Open questions at the time
    • Direct SNARE partners for exosome/CD36 routes incompletely mapped
    • Hrd1-VAMP3 ubiquitylation site not pinpointed
  19. 2021 Medium

    Defined VAMP3 as the exocytic SNARE for astrocyte BDNF release and as a host target hijacked by chlamydial Inc proteins, illustrating selectivity and pathogen subversion.

    Evidence QD-BDNF live tracking with Vamp3 KD; inducible FLAG-Inc expression and Co-IP/localization in C. trachomatis infection

    PMID:33229367 PMID:34707216

    Open questions at the time
    • BDNF-loading SNARE partners undefined
    • Functional consequence of Inc-VAMP3 interaction for infection unresolved
  20. 2022 Medium

    Showed VAMP3 supports mast cell degranulation and plasma-membrane homeostasis, including homotypic granule fusion and receptor surface expression.

    Evidence shRNA KD with degranulation, CD63-GFP granule imaging, FcεRI surface flow cytometry in RBL-2H3 cells

    PMID:35990647

    Open questions at the time
    • Direct vs indirect effects on lipid rafts/endocytosis not separated
    • SNARE partners in mast cell granules not defined
  21. 2023 High

    Established in vivo that macrophage VAMP3 drives inflammatory cytokine secretion and contributes to inflammatory pain, and identified galectin-9 as a partner rerouting VAMP3 vesicles for secretion.

    Evidence Myeloid-specific Vamp3 KO with cytokine, edema, and pain assays; galectin-9 IP-MS, KD, and cytokine secretion in dendritic cells

    PMID:37755527 PMID:37965323

    Open questions at the time
    • How galectin-9 mechanistically diverts vesicles from lysosomal degradation incomplete
  22. 2025 High

    Integrated VAMP3 regulation into a phosphorylation-gated, WDFY2-chaperoned secretion switch, defined its role in BBB transcytosis and bacterial brain penetration, and connected its mRNA m6A regulation to gastric cancer and melanosome maturation.

    Evidence Phosphoproteomics with VAMP3 phospho-mutants, WDFY2/STX4 Co-IP and TIRF IL-6 imaging; VAMP3-syntaxin4 Co-IP with KO mice and transcytosis/penetration assays; METTL14 m6A and ATF3 modulation in cancer; BoNT/DC cleavage and KD in melanocytes

    PMID:39827141 PMID:40286827 PMID:40601634 PMID:40977280

    Open questions at the time
    • Specific kinase phosphorylating VAMP3 not identified
    • m6A reader linking modification to VAMP3 translation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How VAMP3's many context-specific SNARE partner choices and post-translational marks (ubiquitin, phosphorylation, m6A) are integrated to select among its diverse cargo and fusion destinations remains unresolved.
  • No structural model of VAMP3 ternary complexes across its partner repertoire
  • Kinase(s), DUBs, and m6A readers acting on VAMP3 unidentified
  • Rules governing cargo-specific SNARE pairing not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0060090 molecular adaptor activity 4
Localization
GO:0005768 endosome 4 GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 3 R-HSA-9612973 Autophagy 2
Partners
LGALS9PI4K2ARAB8ASNAP23STX4STX6VTI1BWDFY2
Complex memberships
STX6-VTI1B-VAMP3 SNARE complexVAMP3/syntaxin4/SNAP23 SNARE complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 VAMP3-containing vesicles, likely derived from recycling endosomes, focally accumulate at sites of nascent phagosome formation, and polarized fusion of VAMP3 vesicles with the plasma membrane precedes phagosome sealing, indicating VAMP3 mediates targeted endomembrane delivery to elongate pseudopods during phagocytosis. GFP-tagging as fluorescent indicator and exofacial epitope; live fluorescence microscopy; focal exocytosis assay in macrophages The Journal of cell biology Medium 10791982
1997 VAMP3/cellubrevin functions as a vesicle SNARE (v-SNARE) pairing with the t-SNARE syntaxin 4 to mediate insulin-stimulated GLUT4 vesicle translocation to the plasma membrane in adipocytes; expression of the cytoplasmic domain of VAMP3 inhibited insulin-stimulated GLUT4 translocation, and syntaxin 4 co-immunoprecipitated GLUT4-containing vesicles in an insulin-dependent manner. Dominant-negative cytoplasmic domain expression via recombinant vaccinia virus or microinjection; co-immunoprecipitation of GLUT4 vesicles with syntaxin 4 cytoplasmic domain Molecular and cellular biology Medium 9111311
2000 VAMP2, but not VAMP3/cellubrevin, is required for insulin-stimulated GLUT4 translocation in L6 myoblasts; only tetanus-toxin-resistant VAMP2 (not VAMP3) rescued inhibition of insulin-dependent GLUT4 translocation, and insulin-induced cortical actin reorganization clustered GLUT4 with VAMP2 but not VAMP3. Tetanus toxin light chain transfection to cleave VAMP2/VAMP3; rescue with toxin-resistant SNARE constructs; single-cell fluorescence GLUT4 translocation assay; actin/SNARE co-localization imaging Molecular biology of the cell High 10888677
2001 VAMP3 null mice display normal insulin-stimulated and exercise-regulated GLUT4 translocation, normal glucose tolerance, and normal general membrane trafficking (phagocytosis, pinocytosis, transferrin receptor recycling), demonstrating VAMP3 is not essential for these processes in vivo. Targeted gene disruption (VAMP3 knockout mice); glucose uptake assays in primary adipocytes and skeletal muscle; phagocytosis, pinocytosis, and transferrin recycling assays Molecular and cellular biology High 11238894
2002 VAMP3 and VAMP8 are the VAMP isoforms present in human platelets and form SNARE complexes with syntaxin 4; recombinant VAMP3 (but not VAMP2) blocked alpha-granule secretion and nearly completely inhibited dense-granule secretion in permeabilized platelets, demonstrating VAMP3 is required for platelet granule secretion. Mass spectrometry co-immunoprecipitation (nano-LC-MS/MS) from platelets with syntaxin 4; recombinant VAMP competition assay in streptolysin O-permeabilized platelets; flow cytometry (P-selectin) and radiolabel serotonin release Blood High 12130530
2002 VAMP3-null macrophages show transiently slower uptake of zymosan (but not IgG-beads, complement-opsonized particles, or latex microspheres) at early time points (5–15 min), indicating VAMP3 modulates efficient zymosan uptake but is not absolutely required for phagocytosis. VAMP3 knockout mouse-derived bone marrow macrophages; phagocytosis assays with multiple particles; phagosome maturation assay (LAMP-1 acquisition) Journal of leukocyte biology Medium 12101283
2007 VAMP3 forms fusogenic SNARE complexes with syntaxin1/SNAP-25, syntaxin1/SNAP-23, and syntaxin4/SNAP-25, but not with syntaxin4/SNAP-23; deletion of the N-terminal domain of syntaxin4 enhanced membrane fusion more than two-fold, indicating this domain negatively regulates fusion. Cell fusion assay using full-length SNARE proteins expressed in cells; deletion mutagenesis of syntaxin4 N-terminal domain Experimental cell research Medium 17651732
2009 VAMP3 (v-SNARE) is required for fusion of multivesicular bodies (MVBs) with autophagosomes to generate amphisomes in K562 cells; knockdown of VAMP3 blocked this MVB-autophagosome fusion step but did not affect subsequent fusion with lysosomes, which instead requires VAMP7. siRNA knockdown; morphological, molecular, and biochemical analyses of autophagosome/MVB fusion in K562 cells Biochimica et biophysica acta Medium 19781582
2009 VAMP3 co-localizes with MMP2, MMP9, and MT1-MMP in HT-1080 fibrosarcoma cells; dominant-negative VAMP3 mutants, RNAi, and tetanus toxin cleavage of VAMP3 impaired secretion of MMP2/MMP9, trafficking of MT1-MMP to the cell surface, gelatin degradation, and cell invasion. Dominant-negative SNARE expression; siRNA/RNAi; tetanus toxin; co-localization by immunofluorescence; gelatin degradation assay; Boyden chamber invasion assay Journal of cell science High 19910495
2009 VAMP3 silencing reduces beta1-integrin levels at the cell surface (without affecting total integrin) and inhibits chemotactic cell migration by >60%, establishing VAMP3 as required for trafficking of beta1-integrin to the plasma membrane and for cell migration. siRNA knockdown; flow cytometry (surface beta1-integrin); chemotaxis migration assay Biochemical and biophysical research communications Medium 19159614
2010 VAMP3 (but not VAMP8) is present on Weibel-Palade bodies (WPBs) and forms a stable SNARE complex with syntaxin 4 and SNAP23 in endothelial cells; soluble VAMP3 cytoplasmic domain mutants (but not VAMP8 mutants) interfere with Ca2+-triggered vWF secretion from permeabilized endothelial cells. Immunofluorescence co-localization; co-immunoprecipitation; permeabilized endothelial cell secretion assay with dominant-negative SNARE mutants; immunoblotting Biochimica et biophysica acta High 21094665
2011 VAMP3 mediates fusion of recycling-endosome-derived vesicles carrying PLP with the oligodendroglial plasma membrane; Syntaxin-4 was identified as the prime acceptor Q-SNARE for VAMP3 in this context. Interference with VAMP3 by siRNA or dominant-negative expression diminished PLP transport to the cell surface. siRNA knockdown; dominant-negative VAMP3 expression; co-localization; VAMP3-deficient mice; mocha mutant mice analysis The Journal of neuroscience Medium 21490207
2011 The VAMP3/Stx4/SNAP23 SNARE complex regulates macrophage adhesion, spreading, and persistent migration on fibronectin by mediating polarized exocytosis of VAMP3-positive recycling endosome membrane; reduction of VAMP3 disrupted podosome superstructure organization and polarized podosome localization during migration. shRNA knockdown and overexpression; live-cell and fixed immunofluorescence; cell spreading and migration assays on fibronectin Experimental cell research Medium 21586284
2012 VAMP3 and syntaxin 6 (STX6) form a v-/t-SNARE complex; endocytosed alpha3beta1-integrin traffics through VAMP3-containing recycling endosomes before delivery via STX6-containing trans-Golgi network compartments to the plasma membrane. VAMP3 is required for alpha3beta1-integrin delivery to the cell surface. Co-immunoprecipitation of VAMP3-STX6 complex; siRNA knockdown; immunofluorescence co-localization; integrin surface delivery assay; chemotaxis migration assay Journal of cell science Medium 22573826
2013 VAMP3 is a direct ubiquitylation target of goliath-family E3 ubiquitin ligases (Drosophila Goliath/Godzilla, human RNF167); ubiquitylation of VAMP3 by Godzilla/RNF167 abrogates normal recycling endosome trafficking, and mutation of Godzilla ubiquitylation target lysines on VAMP3 blocks formation of enlarged Rab5-positive endosomes. Ubiquitylation assays; site-directed mutagenesis of VAMP3 lysines; overexpression and loss-of-function in Drosophila and mammalian cells; endosome morphology analysis The EMBO journal High 23353890
2013 VAMP3 and SNAP23 mediate Ca2+-dependent secretion of IL-6 and TNFα from synovial sarcoma cells; a VAMP3 antibody co-precipitated SNAP23 and syntaxin-2 (and syntaxin-3 to a lesser extent), and SNAP23/VAMP3 form SDS-resistant complexes that are disrupted upon SNAP23 knockdown. siRNA knockdown; ELISA cytokine secretion assay; co-immunoprecipitation; SDS-resistant SNARE complex assay The FEBS journal Medium 24373201
2014 Phosphatidylinositol 4-kinase IIα (PI4K2A) physically interacts with VAMP3 on tubulo-vesicular endosomes; PI4K2A knockdown inhibits VAMP3 trafficking to perinuclear membranes, impairs VAMP3-mediated transferrin receptor recycling, and decreases VAMP3 association with its cognate Q-SNARE Vti1a. Acute depletion of PtdIns4P on endosomes significantly delays VAMP3 trafficking. Co-immunoprecipitation; MS interactome; siRNA knockdown; transferrin receptor recycling assay; co-localization; acute PtdIns4P depletion Journal of cell science High 25002402
2014 VAMP3 is required for efficient entry of Uukuniemi virus (bunyavirus) into cells; viruses enter VAMP3-positive endosomal vesicles within 5 min of internalization; in VAMP3-depleted cells, viruses are trapped in LAMP1-negative compartments. Tetanus toxin cleavage of VAMP3 blocks infection. Genome-wide siRNA screens (two independent libraries); siRNA-mediated VAMP3 depletion; tetanus toxin inactivation; fluorescence live and fixed-cell imaging; LAMP1 co-localization Journal of virology High 24850728
2015 Rab8 is required for VAMP3 clustering at the immune synapse in T cells; in dominant-negative Rab8 T cells, TCR-positive endosomes polarized normally to the synapse but could not dock/fuse because VAMP3 failed to cluster there. VAMP3 also interacts with Rab8 at the base of the cilium in NIH-3T3 cells. Dominant-negative Rab8 expression; immunofluorescence co-localization; TCR recycling assay at the immune synapse; co-localization of VAMP3 with Rab8 in cilia Journal of cell science Medium 26034069
2015 VAMP3 vesicles in cortical astrocytes undergo Ca2+-independent exo-endocytotic cycling at the plasma membrane and regulate the recycling/surface expression of plasma membrane glutamate transporters; cAMP modulates VAMP3 vesicle cycling and glutamate uptake. Astrocytes express VAMP3 but not VAMP2. VAMP2 and VAMP3 knockout mice; STED and TIRF microscopy; single-vesicle imaging; glutamate uptake assay; optogenetics and pharmacology to modulate cAMP The Journal of physiology High 25864578
2015 VAMP2, VAMP3, and VAMP8 are internalized via clathrin-independent endocytosis stimulated by Shiga toxin; Shiga toxin increases VAMP3 uptake even when clathrin-dependent endocytosis is blocked, and toxin trafficking/intoxication relies on these SNAREs. Fluorescence imaging of VAMP internalization; clathrin inhibition; Shiga toxin trafficking assays; intoxication assays Journal of cell science Medium 26071526
2016 VAMP3 interacts with NKCC2 co-transporter and co-localizes at the TAL apical surface; in vivo silencing of VAMP3 blocks constitutive (but not cAMP-stimulated) NKCC2 exocytic delivery to the apical membrane. VAMP3 knockout mice show decreased NKCC2 expression, increased urinary electrolyte/water excretion, and lower blood pressure. Co-immunoprecipitation (VAMP3-NKCC2); in vivo siRNA silencing in rat TAL; surface biotinylation; exocytic delivery assay; VAMP3 knockout mice; blood pressure measurement The Journal of biological chemistry High 27551042
2016 The STX6-VTI1B-VAMP3 SNARE complex forms on recycling endosomes and is required for fusion between recycling endosomes (REs) and GAS-containing autophagosome-like vacuoles (GcAVs) during xenophagy; STX6 localizes to GcAVs via tyrosine-based sorting motif and H2 SNARE domain; RABGEF1 mediates the RE-GcAV fusion through this complex. Co-immunoprecipitation of SNARE complex; siRNA knockdown and CRISPR knockout of STX6, VAMP3, VTI1B; GAS xenophagy assay; co-localization by immunofluorescence Autophagy High 27791468
2017 VAMP3 and SNAP23 mediate disturbed-flow (oscillatory shear)-induced endothelial secretion of miR-126-3p and other microRNAs into non-membrane-bound extracellular form; knockdown of VAMP3/SNAP23 reduces endothelial miRNA secretion and SMC proliferation/migration. mTORC1 inhibition blocks this secretion via transcriptional suppression of VAMP3 and SNAP23. siRNA knockdown; shear stress in vitro system; qPCR/miRNA quantification; SMC co-culture proliferation/migration assays; in vivo rapamycin treatment; carotid artery ligation model Proceedings of the National Academy of Sciences of the United States of America High 28716920
2017 VAMP3/Syb (Drosophila ortholog) and YKT6 are required for constitutive secretory carrier fusion with the plasma membrane; combinatorial RNAi depletion in Drosophila cells identified SNARE complexes including STX1/SNAP24/29/Syb; RNAi depletion of YKT6 and VAMP3 in mammalian cells also blocked constitutive secretion. Quantitative secretion assay; combinatorial RNAi depletion in Drosophila S2 cells and mammalian cells PLoS genetics Medium 28403141
2019 WDFY2 physically interacts with VAMP3 on endosomal tubules enriched in PtdIns3P; WDFY2 knockout causes redistribution of VAMP3 into small vesicles near the plasma membrane, leading to increased VAMP3-dependent secretion of MT1-MMP, enhanced ECM degradation, and increased cell invasion. Co-immunoprecipitation (WDFY2-VAMP3 interaction); CRISPR knockout of WDFY2; immunofluorescence redistribution of VAMP3; MT1-MMP secretion assay; ECM degradation assay; invasion assay Nature communications High 31253801
2020 bFGF signaling increases VAMP3 abundance on neuronal extracellular vesicles and enhances MVB-plasma membrane fusion in hippocampal neurons; VAMP3 knockdown attenuates bFGF-induced EV release, establishing VAMP3 as mediating bFGF-regulated neuronal exosome secretion. Patch-clamp electrophysiology with pH-sensitive dye imaging of MVB-PM fusion; proteomics of neuronal EVs; siRNA knockdown; nanoparticle tracking Advanced science Medium 32195080
2020 VAMP3 and SNAP23 mediate oscillatory shear-induced endothelial VWF secretion; oscillatory shear promotes translocation of VAMP3 and SNAP23 to the plasma membrane; knockdown of VAMP3/SNAP23 reduces VWF secretion and platelet aggregation, and systemic VAMP3/SNAP23 inhibition ameliorates FeCl3-induced thrombogenesis in mice. siRNA knockdown; intracellular localization by immunofluorescence; VWF ELISA; platelet aggregation assay; in vivo carotid artery thrombosis model (FeCl3); intraluminal overexpression Frontiers in cell and developmental biology Medium 33224946
2020 Hrd1 E3 ubiquitin ligase ubiquitylates VAMP3, and H2S promotes Hrd1 S-sulfhydration at Cys115, which enhances VAMP3 ubiquitylation and prevents CD36 translocation to the plasma membrane; Hrd1 Cys115 mutation abolished VAMP3 ubiquitylation and increased CD36/VAMP3 plasma membrane expression and lipid droplet formation. S-sulfhydration assay; immunoprecipitation for ubiquitylation; LC-MS/MS; site-directed mutagenesis (Hrd1 Cys115); siRNA knockdown; Western blot; lipid droplet staining Aging and disease Medium 32257542
2021 VAMP3 in astrocytes selectively mediates the exocytosis of endocytosed BDNF; endocytic QD-BDNF particles are enriched in Vamp3-positive vesicles, and Vamp3 downregulation disrupts BDNF secretion without affecting BDNF uptake or intracellular transport. Quantum dot-conjugated BDNF (QD-BDNF) live tracking in cultured astrocytes; siRNA knockdown of Vamp3; confocal imaging of ATP-evoked exocytosis Scientific reports Medium 34707216
2021 Five chlamydial inclusion membrane proteins (Incs) transiently and temporally interact with VAMP3 during Chlamydia trachomatis infection; loss of incA or ct813 expression altered VAMP3 localization to the inclusion. VAMP3 (and VAMP4) are recruited to the chlamydial inclusion during mid-developmental cycle requiring de novo chlamydial protein synthesis. Inducible FLAG-Inc expression in C. trachomatis transformants; co-immunoprecipitation; immunofluorescence localization in infected cells; two complementary experimental systems Infection and immunity Medium 33229367
2022 VAMP3 in mast cells (RBL-2H3) mediates secretory granule fusion and degranulation upon FcεRI activation; VAMP3 knockdown decreases degranulation, impairs CD63-marked granule enlargement (homotypic fusion), and reduces FcεRI surface expression by disrupting plasma membrane homeostasis. VAMP3 KD also dysregulates endocytosis and lipid raft formation. shRNA-mediated VAMP3 knockdown; degranulation assay; CD63-GFP fluorescence granule imaging; flow cytometry (FcεRI surface expression); intracellular Ca2+ response; cytokine ELISA Frontiers in immunology Medium 35990647
2023 Galectin-9 physically interacts with VAMP3 (identified by immunoprecipitation-mass spectrometry) in dendritic cells; galectin-9 depletion causes cytokine-containing vesicles to accumulate in the Golgi and undergo lysosomal degradation rather than being secreted, and galectin-9 is required for rerouting VAMP3-containing endosomes upon DC activation. Immunoprecipitation-mass spectrometry (galectin-9 interactome); siRNA knockdown; immunofluorescence (vesicle accumulation in Golgi); cytokine secretion assay Cellular and molecular life sciences Medium 37755527
2023 Myeloid-specific VAMP3 knockout (LysM-Cre x Vamp3-flox) mice show significantly reduced TNF-α and IL-6 release from macrophages, decreased CFA-induced paw edema, and reduced mechanical allodynia and thermal hyperalgesia, demonstrating VAMP3 in macrophages mediates inflammatory cytokine secretion and contributes to inflammatory pain. Conditional myeloid-specific Vamp3 knockout mice; ELISA cytokine measurement; CFA inflammatory pain model; behavioral pain assays; RT-qPCR Frontiers in immunology High 37965323
2025 VAMP3 on transferrin receptor (TfR) vesicles interacts with the t-SNARE syntaxin 4 (restricted to the basolateral membrane of HBMECs) to mediate fusion of TfR transcytotic vesicles with the basolateral membrane; silencing VAMP3 reduces TfR transcytosis and NMEC brain penetration in vitro and in vivo; NMEC infection upregulates VAMP3 and syntaxin 4 via TLR4-TRAM-TRIF-TRAF3-IKK-IRF3 signaling to enhance transcytosis. Co-immunoprecipitation (VAMP3-syntaxin 4); siRNA knockdown and overexpression in BBB model; VAMP3 KO mice; transferrin transcytosis assay; NMEC brain penetration assay; signaling pathway inhibitors Proceedings of the National Academy of Sciences of the United States of America High 40601634
2025 Phosphorylation of VAMP3 (upon LPS stimulation of dendritic cells) releases VAMP3 from the chaperone WDFY2, enabling IL-6-positive VAMP3-positive vesicles to traffic to and fuse with the plasma membrane via complex formation with STX4, mediating IL-6 secretion in a polarized manner. Quantitative TIRF microscopy; phosphoproteomic bioinformatic analysis; VAMP3 phospho-mutants; co-immunoprecipitation (VAMP3-WDFY2, VAMP3-STX4); IL-6 secretion assay; LPS stimulation of dendritic cells Journal of cell science High 40977280
2025 H. pylori reduces METTL14-mediated m6A modification of VAMP3 mRNA (via upregulation of ATF3 suppressing METTL14), decreasing VAMP3 expression and promoting c-Met recycling via VAMP3/LC3C pathway, thereby accelerating gastric cancer progression. m6A modification assay; METTL14 knockdown/overexpression; ATF3 modulation; co-immunoprecipitation; in vitro/in vivo cancer cell proliferation/metastasis assays Cell death discovery Medium 39827141
2025 Botulinum neurotoxin type DC (BoNT/DC) cleaves VAMP3 (and VAMP2) in melanocytes; VAMP3 knockdown (but not VAMP2 knockdown) reduces melanin content and arrests melanosome maturation at stage II (more early, fewer late-stage IV melanosomes), establishing VAMP3 as required for cargo (tyrosinase/PMEL) trafficking during melanogenesis. BoNT/DC cleavage of VAMPs; siRNA knockdown of VAMP3 and VAMP2; melanin content assay; electron microscopy of melanosome stages; multiple human melanocyte models Toxicon Medium 40286827

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochimica et biophysica acta 395 19781582
2000 Focal exocytosis of VAMP3-containing vesicles at sites of phagosome formation. The Journal of cell biology 255 10791982
1997 Syntaxin 4, VAMP2, and/or VAMP3/cellubrevin are functional target membrane and vesicle SNAP receptors for insulin-stimulated GLUT4 translocation in adipocytes. Molecular and cellular biology 205 9111311
2013 The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10. Human molecular genetics 171 23813974
2002 Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion. Blood 118 12130530
2009 VAMP3, syntaxin-13 and SNAP23 are involved in secretion of matrix metalloproteinases, degradation of the extracellular matrix and cell invasion. Journal of cell science 96 19910495
2000 VAMP2, but not VAMP3/cellubrevin, mediates insulin-dependent incorporation of GLUT4 into the plasma membrane of L6 myoblasts. Molecular biology of the cell 96 10888677
2008 Vesicle associated membrane protein (VAMP)-7 and VAMP-8, but not VAMP-2 or VAMP-3, are required for activation-induced degranulation of mature human mast cells. European journal of immunology 85 18253931
1996 A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk' metastatic non-seminomatous germ cell tumors. Annals of oncology : official journal of the European Society for Medical Oncology 79 9037359
2001 VAMP3 null mice display normal constitutive, insulin- and exercise-regulated vesicle trafficking. Molecular and cellular biology 72 11238894
2020 LncRNA PVT1 promotes exosome secretion through YKT6, RAB7, and VAMP3 in pancreatic cancer. Aging 70 32499447
2012 Regulation of integrin endocytic recycling and chemotactic cell migration by syntaxin 6 and VAMP3 interaction. Journal of cell science 70 22573826
2011 Transport of the major myelin proteolipid protein is directed by VAMP3 and VAMP7. The Journal of neuroscience : the official journal of the Society for Neuroscience 67 21490207
2019 miR-124/VAMP3 is a novel therapeutic target for mitigation of surgical trauma-induced microglial activation. Signal transduction and targeted therapy 62 31637007
2015 The small GTPase Rab8 interacts with VAMP-3 to regulate the delivery of recycling T-cell receptors to the immune synapse. Journal of cell science 60 26034069
2010 VAMP3 is associated with endothelial weibel-palade bodies and participates in their Ca(2+)-dependent exocytosis. Biochimica et biophysica acta 57 21094665
2020 Fibroblast Growth Factor 2-Mediated Regulation of Neuronal Exosome Release Depends on VAMP3/Cellubrevin in Hippocampal Neurons. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 54 32195080
2014 Endosomal sorting of VAMP3 is regulated by PI4K2A. Journal of cell science 54 25002402
2004 High-dose CEB vs BEAM with autologous stem cell transplant in lymphoma. Bone marrow transplantation 49 15273714
2014 Genome-wide small interfering RNA screens reveal VAMP3 as a novel host factor required for Uukuniemi virus late penetration. Journal of virology 48 24850728
2017 VAMP3 and SNAP23 mediate the disturbed flow-induced endothelial microRNA secretion and smooth muscle hyperplasia. Proceedings of the National Academy of Sciences of the United States of America 44 28716920
2013 Goliath family E3 ligases regulate the recycling endosome pathway via VAMP3 ubiquitylation. The EMBO journal 44 23353890
2016 The STX6-VTI1B-VAMP3 complex facilitates xenophagy by regulating the fusion between recycling endosomes and autophagosomes. Autophagy 39 27791468
2021 Circ_0002984 induces proliferation, migration and inflammation response of VSMCs induced by ox-LDL through miR-326-3p/VAMP3 axis in atherosclerosis. Journal of cellular and molecular medicine 37 34169652
2015 Astrocyte VAMP3 vesicles undergo Ca2+ -independent cycling and modulate glutamate transporter trafficking. The Journal of physiology 37 25864578
2009 Silencing of VAMP3 inhibits cell migration and integrin-mediated adhesion. Biochemical and biophysical research communications 37 19159614
2017 VAMP3/Syb and YKT6 are required for the fusion of constitutive secretory carriers with the plasma membrane. PLoS genetics 35 28403141
2019 WDFY2 restrains matrix metalloproteinase secretion and cell invasion by controlling VAMP3-dependent recycling. Nature communications 34 31253801
2002 Rate and extent of phagocytosis in macrophages lacking vamp3. Journal of leukocyte biology 34 12101283
2020 Exogenous H2S Induces Hrd1 S-sulfhydration and Prevents CD36 Translocation via VAMP3 Ubiquitylation in Diabetic Hearts. Aging and disease 32 32257542
2011 VAMP3 regulates podosome organisation in macrophages and together with Stx4/SNAP23 mediates adhesion, cell spreading and persistent migration. Experimental cell research 32 21586284
2007 Membrane fusion by VAMP3 and plasma membrane t-SNAREs. Experimental cell research 32 17651732
2014 Vesicle-associated membrane protein 2 (VAMP2) but Not VAMP3 mediates cAMP-stimulated trafficking of the renal Na+-K+-2Cl- co-transporter NKCC2 in thick ascending limbs. The Journal of biological chemistry 30 25008321
2013 SNAP-23 and VAMP-3 contribute to the release of IL-6 and TNFα from a human synovial sarcoma cell line. The FEBS journal 25 24373201
2021 Endocytic BDNF secretion regulated by Vamp3 in astrocytes. Scientific reports 23 34707216
2000 Binding characteristics of CebR, the regulator of the ceb operon required for cellobiose/cellotriose uptake in Streptomyces reticuli. FEMS microbiology letters 22 10981702
2021 Eukaryotic SNARE VAMP3 Dynamically Interacts with Multiple Chlamydial Inclusion Membrane Proteins. Infection and immunity 20 33229367
2023 Galectin-9 interacts with Vamp-3 to regulate cytokine secretion in dendritic cells. Cellular and molecular life sciences : CMLS 19 37755527
2016 Vesicle-associated Membrane Protein 3 (VAMP3) Mediates Constitutive Trafficking of the Renal Co-transporter NKCC2 in Thick Ascending Limbs: ROLE IN RENAL FUNCTION AND BLOOD PRESSURE. The Journal of biological chemistry 18 27551042
2015 Shiga toxin stimulates clathrin-independent endocytosis of the VAMP2, VAMP3 and VAMP8 SNARE proteins. Journal of cell science 15 26071526
2022 Multifunctional regulation of VAMP3 in exocytic and endocytic pathways of RBL-2H3 cells. Frontiers in immunology 14 35990647
2023 Myeloid Vamp3 deletion attenuates CFA-induced inflammation and pain in mice via ameliorating macrophage infiltration and inflammatory cytokine production. Frontiers in immunology 13 37965323
2025 Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling. Cell death discovery 10 39827141
2012 Silencing of VAMP3 expression does not affect Brucella melitensis infection in mouse macrophages. Virulence 8 23076244
2006 Auto-antibodies in prostate cancer: humoral immune response to antigenic determinants coded by the differentially expressed transcripts FLJ23438 and VAMP3. The Prostate 8 16897729
2020 VAMP3 and SNAP23 as Potential Targets for Preventing the Disturbed Flow-Accelerated Thrombus Formation. Frontiers in cell and developmental biology 7 33224946
2015 Complete Genome Sequence of Pseudomonas aeruginosa Phage vB_PaeM_CEB_DP1. Genome announcements 7 26404589
2023 miR-124 and VAMP3 Act Antagonistically in Human Neuroblastoma. International journal of molecular sciences 5 37834325
2022 VAMP3 and VAMP8 Regulate the Development and Functionality of Parasitophorous Vacuoles Housing Leishmania amazonensis. Infection and immunity 5 35130453
2021 Human VAMP3 Suppresses or Negatively Regulates Bax Induced Apoptosis in Yeast. Biomedicines 5 33478086
1998 Pharmacological profile of CEB-1957 and atropine toward brain muscarinic receptors and comparative study of their efficacy against sarin poisoning. Toxicology and applied pharmacology 5 9653063
2025 Vamp3/syntaxin 4 mediates the basolateral membrane fusion of TfR transcytosis across the BBB and is exploited by pathogenic E. coli. Proceedings of the National Academy of Sciences of the United States of America 2 40601634
2025 Effects of combined estrogen and bazedoxifene (CEB) on depressive symptoms in perimenopause. Journal of affective disorders 1 40633782
2025 Phosphorylation of VAMP3 couples IL-6 exocytosis to dendritic cell activation. Journal of cell science 1 40977280
2022 High-Pressure Synthesis of Light Lanthanide Dodecaborides (PrB12 and CeB12): Effects of Valence Fluctuation on Volume and Formation Pressure. Inorganic chemistry 1 35078311
2019 Identification of the impurity phase in high-purity CeB6 by convergent-beam electron diffraction. Acta crystallographica. Section A, Foundations and advances 1 31041905
2002 Field-induced magnetization distribution and antiferroquadrupolar order in CeB(6). Physical review letters 1 12144414
2025 Botulinum neurotoxin type DC (BoNT/DC) cleavage of VAMP3 reduces melanin production in melanocytes. Toxicon : official journal of the International Society on Toxinology 0 40286827
2025 Exosomal miR-152-5p promotes trophoblast apoptosis by inhibiting the PI3K/AKT/FOXO3a signaling pathway via targeting VAMP3 in gestational diabetes mellitus. Placenta 0 41124982

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