Affinage

VAMP1

Vesicle-associated membrane protein 1 · UniProt P23763

Length
118 aa
Mass
12.9 kDa
Annotated
2026-04-28
31 papers in source corpus 11 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VAMP1 (synaptobrevin 1) is a vesicle-associated v-SNARE that drives membrane fusion and regulated exocytosis by forming a ternary SNARE complex with syntaxin and SNAP-25. At the neuromuscular junction, VAMP1 is essential for Ca²⁺-triggered neurotransmitter release: its genetic loss reduces evoked and spontaneous transmission, decreases calcium sensitivity and cooperativity, and causes pronounced release asynchrony without altering the readily releasable vesicle pool size (PMID:21282288). In the central nervous system, VAMP1 is preferentially expressed in inhibitory GABAergic interneurons, where its mRNA is stabilized by RBFOX1 and RBFOX3 through suppression of microRNA-9; loss of these regulators depletes VAMP1, impairs inhibitory neurotransmission, and produces seizures that are rescued by VAMP1 re-expression (PMID:29621484, PMID:35951651). Alternative splicing generates isoforms with distinct C-terminal sequences that determine subcellular targeting—VAMP1A to the plasma membrane and VAMP1B to mitochondria—with targeting governed by the length of the hydrophobic anchor and the addition of C-terminal positive charges (PMID:9658161).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1988 High

    Establishing that VAMP1 is a synaptic vesicle integral membrane protein with a cytoplasm-facing topology resolved the fundamental question of where this molecule sits and how it might interact with cytoplasmic fusion machinery.

    Evidence cDNA cloning from Torpedo electromotor nucleus library plus tryptic digestion topology assays on intact vs. lysed vesicles

    PMID:3380805

    Open questions at the time
    • No functional fusion assay performed
    • Binding partners on the target membrane not identified
    • Role of individual structural domains not mapped
  2. 1998 High

    Demonstrating that alternative splicing generates VAMP1 isoforms with distinct C-terminal sequences that direct differential subcellular targeting (plasma membrane vs. mitochondria) revealed how a single gene could serve different membrane compartments.

    Evidence Epitope-tagged VAMP1A and VAMP1B constructs transfected into endothelial cells with fluorescence localization and C-terminal mutagenesis

    PMID:10544008 PMID:9658161

    Open questions at the time
    • Functional role of mitochondrial VAMP1B isoform unknown
    • Targeting determinants not validated in neurons
    • Full functional characterization of all six reported splice isoforms lacking
  3. 2010 Medium

    Showing that VAMP1 co-sediments with ANP granules and forms a SNARE complex with syntaxin-4 in cardiac atrial myocytes, with its knockdown blocking ANP release, extended the functional role of VAMP1 beyond neurons to regulated exocytosis in cardiomyocytes.

    Evidence Co-sedimentation, co-localization microscopy, siRNA knockdown with ANP release measurement in cardiac atrial myocytes

    PMID:20801128

    Open questions at the time
    • Single-lab finding; independent replication needed
    • Relative contribution of VAMP1 vs. VAMP2 to ANP release not resolved
    • In vivo cardiac relevance not tested
  4. 2010 Medium

    Reconstitution studies revealed that anionic lipids control VAMP1 secondary structure and orientation at membrane interfaces, providing biophysical insight into how the lipid environment modulates SNARE conformation prior to fusion.

    Evidence Lipid monolayer reconstitution at air-water interface with infrared spectroscopy

    PMID:20085749

    Open questions at the time
    • Relevance to native synaptic vesicle membranes not established
    • Effect on actual SNARE complex assembly kinetics not measured
    • Single in vitro system
  5. 2011 High

    Genetic ablation of VAMP1 in mice established its non-redundant role at the NMJ by showing that loss impairs calcium sensitivity, cooperativity, and synchrony of release without reducing the readily releasable pool, pinpointing VAMP1's role in the Ca²⁺-triggered fusion step rather than vesicle docking or priming.

    Evidence Nonsense-mutation knockout mice with comprehensive NMJ electrophysiology including paired-pulse facilitation and calcium cooperativity analysis

    PMID:21282288

    Open questions at the time
    • Whether VAMP2 compensates at central synapses not addressed
    • Molecular basis for altered calcium cooperativity not determined
    • Interaction with calcium sensor (synaptotagmin) not directly tested
  6. 2014 Medium

    Identification of calcineurin/NFAT-mediated transcriptional repression of Vamp1 downstream of plasma membrane Ca²⁺-ATPase depletion revealed a feedback mechanism linking calcium signaling to SNARE gene expression and dopamine secretion.

    Evidence ChIP of NFAT1/3 at Vamp promoters combined with siRNA knockdown of PMCA2/3 and dopamine secretion assays in PC12 cells

    PMID:24667359

    Open questions at the time
    • Relevance to primary neurons or in vivo contexts not shown
    • Whether NFAT regulation is specific to Vamp1 vs. general SNARE control unclear
    • Single-lab study in a neuroendocrine cell line
  7. 2016 High

    Demonstrating that VAMP1 (not VAMP2/3) is specifically required for TNFα-induced TRPV1/TRPA1 surface trafficking and CGRP exocytosis in sensory neurons established isoform-selective SNARE function in pain-related neuropeptide release.

    Evidence VAMP1 knockdown vs. VAMP2/3 knockdown, botulinum toxin cleavage of syntaxin-1 and SNAP-25, calcium imaging in cultured sensory neurons

    PMID:26888187

    Open questions at the time
    • In vivo pain behavior consequences not assessed
    • Mechanism determining VAMP1 isoform selectivity over VAMP2 unknown
    • Whether VAMP1 directly interacts with TRPV1/TRPA1 cargo not tested
  8. 2018 High

    Showing that RBFOX1 stabilizes Vamp1 mRNA in inhibitory interneurons by blocking microRNA-9 and that VAMP1 re-expression rescues inhibitory transmission deficits established a post-transcriptional regulatory axis controlling excitatory/inhibitory balance through SNARE availability.

    Evidence Conditional Rbfox1 knockout in mice, electrophysiology, Vamp1 knockdown, viral Vamp1 rescue in interneurons, microRNA-9 interaction assays

    PMID:29621484

    Open questions at the time
    • Direct RBFOX1–Vamp1 mRNA binding site not mapped at nucleotide resolution
    • Whether other miRNAs also regulate Vamp1 in this context unknown
    • Relevance to human epilepsy not directly tested
  9. 2022 High

    Extending the RBFOX–VAMP1 axis, RBFOX3/NeuN was shown to regulate Vamp1 preferentially in NPY⁺ GABAergic neurons; its deletion causes seizures and premature mortality rescued by postnatal VAMP1 restoration, establishing VAMP1 as the critical effector of RBFOX3-dependent neuronal excitability control.

    Evidence Conditional Rbfox3 knockout in GABAergic neurons, dentate gyrus electrophysiology, viral VAMP1 rescue, bumetanide pharmacological rescue

    PMID:35951651

    Open questions at the time
    • Whether RBFOX3 acts through the same microRNA-9 mechanism as RBFOX1 not fully resolved
    • Cell-type-specific Vamp1 regulatory elements not defined
    • Contribution of other RBFOX3 targets to the seizure phenotype not excluded

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for VAMP1's differential calcium cooperativity compared to VAMP2, the functional role of the mitochondrial VAMP1B isoform, and whether VAMP1 mutations cause human neuromuscular or neurological disease.
  • No high-resolution structure of VAMP1 in a complete SNARE complex with synaptotagmin
  • Mitochondrial VAMP1B function entirely uncharacterized
  • No human genetic disease formally linked in the provided timeline

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0031410 cytoplasmic vesicle 5 GO:0005886 plasma membrane 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 2
Partners
RBFOX1RBFOX3SNAP25STX1ASTX4STXBP1
Complex memberships
SNARE complex (with syntaxin-1 and SNAP-25)SNARE complex (with syntaxin-4)

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 VAMP1 is a synaptic vesicle-associated integral membrane protein with a cytoplasm-facing topology, consisting of a proline-rich amino terminus, a highly charged internal region, and a hydrophobic C-terminal membrane anchor, suggesting a role in packaging, transport, or release of neurotransmitters. cDNA cloning from Torpedo electromotor nucleus library, tryptic digestion of intact vs. lysed vesicles to determine membrane topology Proceedings of the National Academy of Sciences of the United States of America High 3380805
1998 Alternative splicing of VAMP1 generates isoform VAMP1B, whose C-terminal sequence (shortened hydrophobic anchor plus C-terminal positive charges) directs the protein to mitochondria, whereas VAMP1A localizes to the plasma membrane and endosome-like structures; mitochondrial targeting requires both the addition of positive charge at the C-terminus and a shortened hydrophobic anchor. Transfection of epitope-tagged VAMP1A and VAMP1B constructs into human endothelial cells with fluorescence localization; C-terminal mutagenesis to map targeting determinants Molecular biology of the cell High 9658161
2011 Synaptobrevin1/VAMP1 is essential for Ca2+-triggered neurotransmitter release at the mouse neuromuscular junction (NMJ); loss of VAMP1 reduces both spontaneous and evoked synaptic activities, enhances paired-pulse facilitation, causes pronounced asynchrony in release, and reduces calcium sensitivity and cooperativity, without altering the size of the readily releasable pool. Genetic null mutation (nonsense mutation) in mice; electrophysiology of NMJ synaptic transmission including spontaneous and evoked recordings, paired-pulse facilitation, calcium cooperativity analysis The Journal of physiology High 21282288
2016 VAMP1 (but not VAMP2/3) is required for TNFα-induced surface trafficking of TRPV1 and TRPA1 channels and for CGRP exocytosis from large dense-core vesicles in sensory neurons; this process requires Munc18-1, syntaxin-1, and SNAP-25, forming a SNARE fusion complex at the presynaptic plasma membrane. Co-localization studies in cultured sensory neurons; knockdown/inhibition of VAMP1 vs. VAMP2/3; botulinum neurotoxin cleavage of syntaxin-1 (BoNT/C1) and SNAP-25 (BoNT/A); Ca2+ influx measurement Scientific reports High 26888187
2018 VAMP1 is a vSNARE specifically expressed in inhibitory interneurons and is required for inhibitory synaptic transmission; cytoplasmic RBFOX1 stabilizes Vamp1 mRNA in part by blocking microRNA-9, and loss of RBFOX1 reduces Vamp1 expression, leading to decreased inhibitory neurotransmission and E/I imbalance; re-expression of Vamp1 selectively in interneurons rescues the electrophysiological phenotype. Rbfox1 conditional knockout in mice; electrophysiology of inhibitory synaptic transmission; Vamp1 knockdown; viral rescue (re-expression of Vamp1 in interneurons); microRNA-9 interaction assays Neuron High 29621484
2010 VAMP1 and VAMP2 co-sediment and co-localize with ANP in cardiac atrial myocytes and form a SNARE complex with syntaxin-4; knockdown of VAMP1 or VAMP2 blocks regulated ANP release, demonstrating a role for these VAMPs in cardiac myocyte exocytosis. Co-sedimentation assay, co-localization microscopy, siRNA knockdown of VAMP1/2/3 and syntaxin-4, ANP release measurement Journal of molecular and cellular cardiology Medium 20801128
2001 VAMP1 localizes to membranes of gelatinase and specific secretory granules in human neutrophils and functions as a component of the SNARE complex during exocytosis of these granules. Subcellular fractionation and localization studies in primary human neutrophils Bulletin of experimental biology and medicine Low 11391393
2014 Calcineurin/NFAT signaling, activated downstream of PMCA2 or PMCA3 reduction, represses Vamp1 (and Vamp2) gene expression via NFAT1/NFAT3 transcription factors binding to Vamp gene promoters, leading to impaired SNARE complex formation and reduced dopamine secretion in PC12 neuroendocrine cells. siRNA knockdown of PMCA2/3, chromatin immunoprecipitation (ChIP) of NFAT1/3 at Vamp promoters, calcineurin inhibition, dopamine secretion assay PloS one Medium 24667359
2022 RBFOX3/NeuN regulates Vamp1 expression preferentially in NPY-expressing GABAergic neurons; deletion of Rbfox3 in GABAergic neurons reduces hippocampal Vamp1 expression and causes spontaneous seizures; postnatal restoration of VAMP1 rescues premature mortality and normalizes neuronal excitability in dentate gyrus granule cells. Conditional Rbfox3 knockout in GABAergic neurons; electrophysiology of dentate gyrus granule cells; viral VAMP1 rescue; bumetanide pharmacological rescue Proceedings of the National Academy of Sciences of the United States of America High 35951651
2010 The structure and orientation of VAMP1/synaptobrevin1 at a lipid monolayer interface is controlled by protein-lipid interactions: in neutral lipid (DMPC) or protein-alone monolayers, surface compression drives alpha-helix to beta-sheet transition, whereas anionic lipid (DMPG) inhibits this transition in a concentration-dependent manner and alters protein orientation. Lipid monolayer air-water interface reconstitution with infrared spectroscopy to monitor secondary structure and orientation Biochimica et biophysica acta Medium 20085749
1999 VAMP1 has at least six splice isoforms (VAMP-1A through F) generated by alternative splicing that link conserved exons 1–4 with one of six variable exons (5A–5F) encoding distinct C-terminal sequences, suggesting the C-terminal region has an important role in subcellular vesicle targeting. RT-PCR and cDNA library screening; sequencing of splice variants from human brain, kidney, and inflammatory cells Biochemical and biophysical research communications Low 10544008

Source papers

Stage 0 corpus · 31 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 VAMP-1: a synaptic vesicle-associated integral membrane protein. Proceedings of the National Academy of Sciences of the United States of America 498 3380805
1998 A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal. Molecular biology of the cell 109 9658161
2016 TNFα induces co-trafficking of TRPV1/TRPA1 in VAMP1-containing vesicles to the plasmalemma via Munc18-1/syntaxin1/SNAP-25 mediated fusion. Scientific reports 104 26888187
2018 Rbfox1 Regulates Synaptic Transmission through the Inhibitory Neuron-Specific vSNARE Vamp1. Neuron 77 29621484
2011 The role of synaptobrevin1/VAMP1 in Ca2+-triggered neurotransmitter release at the mouse neuromuscular junction. The Journal of physiology 64 21282288
2006 A null mutation in VAMP1/synaptobrevin is associated with neurological defects and prewean mortality in the lethal-wasting mouse mutant. Neurogenetics 48 17102983
2005 Distribution of synaptobrevin/VAMP 1 and 2 in rat brain. Journal of chemical neuroanatomy 42 16169186
2017 Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome. Annals of neurology 41 28253535
2012 VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland families. American journal of human genetics 41 22958904
2009 Upregulation of NRG-1 and VAMP-1 in human brain aggregates exposed to clozapine. Schizophrenia research 28 19502011
2010 VAMP-1, VAMP-2, and syntaxin-4 regulate ANP release from cardiac myocytes. Journal of molecular and cellular cardiology 25 20801128
2022 Neuronal splicing regulator RBFOX3 mediates seizures via regulating Vamp1 expression preferentially in NPY-expressing GABAergic neurons. Proceedings of the National Academy of Sciences of the United States of America 15 35951651
2021 Prefrontal cortex VAMP1 gene network moderates the effect of the early environment on cognitive flexibility in children. Neurobiology of learning and memory 15 34454100
1999 VAMP-1 has a highly variable C-terminus generated by alternative splicing. Biochemical and biophysical research communications 15 10544008
1997 Tissue-specific alternative RNA splicing of rat vesicle-associated membrane protein-1 (VAMP-1). Gene 14 9358054
2022 Dexmedetomidine Mitigates Microglial Activation Associated with Postoperative Cognitive Dysfunction by Modulating the MicroRNA-103a-3p/VAMP1 Axis. Neural plasticity 13 35494481
2020 Pyrostigmine therapy in a patient with VAMP1-related congenital myasthenic syndrome. Neuromuscular disorders : NMD 12 32616363
2014 Distribution of SNAP25, VAMP1 and VAMP2 in mature and developing deep cerebellar nuclei after estrogen administration. Neuroscience 12 24534378
2014 Calcineurin/NFAT signaling represses genes Vamp1 and Vamp2 via PMCA-dependent mechanism during dopamine secretion by Pheochromocytoma cells. PloS one 10 24667359
2010 Effect of monolayer lipid charges on the structure and orientation of protein VAMP1 at the air-water interface. Biochimica et biophysica acta 9 20085749
2021 Selective Adsorption of Amino Acids in Crystals of Monohydrocalcite Induced by the Facultative Anaerobic Enterobacter ludwigii SYB1. Frontiers in microbiology 8 34394038
2024 Altered Rbfox1-Vamp1 pathway and prefrontal cortical dysfunction in schizophrenia. Molecular psychiatry 6 38273110
2013 The fission yeast synaptobrevin ortholog Syb1 plays an important role in forespore membrane formation and spore maturation. Eukaryotic cell 6 23709180
2024 VAMP1-Related Congenital Myasthenic Syndrome: A Case Report and Literature Review. Neuropediatrics 3 38531369
2023 Altered Rbfox1-Vamp1 pathway and prefrontal cortical dysfunction in schizophrenia. Research square 2 37398467
2008 Identification of a novel Vamp1 splice variant in the cochlear nucleus. Hearing research 2 18655825
2001 Intracellular localization of VAMP-1 protein in human neutrophils. Bulletin of experimental biology and medicine 2 11391393
2024 Expanding the genetic and phenotypic spectrum of congenital myasthenic syndrome: new homozygous VAMP1 splicing variants in 2 novel individuals. Journal of human genetics 1 38355957
2025 Lactobacillus paracasei Activates the KDM3A/VAMP1 Axis to Induce Autophagy in Renal Tubular Epithelial Cells in Chronic Kidney Disease. Probiotics and antimicrobial proteins 0 40111701
2025 The Impact of VAMP1 Mutations on Synaptic Vesicle Fusion Dynamics in Familial Spastic Disorders. Journal of child neurology 0 40856587
2025 Upregulation of miR-151a-5p in high DFI sperm induces DNA damage and mitochondrial dysfunction by targeting INPP4B and VAMP1. Reproductive biology and endocrinology : RB&E 0 41219999