Disease relevance of VAMP1

• A novel tetanus neurotoxin-insensitive vesicle-associated membrane protein in SNARE complexes of the apical plasma membrane of epithelial cells [1].
• Clostridium botulinum type B neurotoxin has been shown to be a zinc endopeptidase specific for vesicle-associated membrane protein (VAMP) [2].
• Decreased capacity of neutrophils to exocytosis in chronic myeloid leukemia is probably caused by the absence of VAMP-1 in these cells [3].
• The demonstration, using BoNTs, of the crucial role of SNAP-25, VAMP and syntaxin in SH-SY5Y cells suggests the use of this neuroblastoma as a model in the study of these proteins in neurotransmitter release [4].
• 50 previously untreated patients with multiple myeloma received two-phase treatment: repeated cycles of 4 day infusion with vincristine, doxorubicin, and methylprednisolone (VAMP) followed by high-dose melphalan (HDM), with autologous bone marrow transplantation where possible [5].

Psychiatry related information on VAMP1

• VAMP: a video activity monitoring processor for the registration of animal locomotor activity [6].

High impact information on VAMP1

• Homologs of the synaptobrevin/VAMP family of synaptic vesicle proteins function on the late secretory pathway in S. cerevisiae [7].
• Botulinum neurotoxin type B (BoNT/B) and tetanus toxin (TeTx) are zinc-dependent proteases that specifically cleave synaptobrevin (VAMP), a membrane protein of synaptic vesicles [8].
• In the recently solved crystal structure of complexin I bound to the synaptic SNARE complex, complexin binds along the groove between the syntaxin and synaptobrevin coils [9].
• When two helix-breaking proline residues are introduced into the juxtamembrane region of VAMP, there is little or no effect on fusion, and the same change in syntaxin 1A only reduced the extent and rate of fusion by half [10].
• Using presynaptic microinjections of botulinum toxins (BoNTs) during paired recordings, we find that cleavage of synaptobrevin in unprimed vesicles leads to an eventual exhaustion of synaptic transmission but does not prevent Gbetagamma-mediated inhibition [11].

Chemical compound and disease context of VAMP1

• In permeabilized ECL cells, addition of calcium results in histamine release, which can be inhibited by tetanus toxin and botulinum neurotoxin A, underlining the functional importance of the synaptosome-associated protein of 25 kDa (SNAP-25) and synaptobrevin [12].
• We have previously shown that the amino-terminal Longin domain of the v-SNARE TI-VAMP (tetanus neurotoxin-insensitive vesicle-associated membrane protein)/VAMP7 plays an inhibitory role in neurite outgrowth [13].
• Starting from the synaptobrevin sequence at the level of the cleavage site by tetanus neurotoxin (Gln76-Phe77), a thiol analogue of glutamine demonstrated inhibitory activities in the millimolar range [14].
• Forty-five patients with relapsed or refractory multiple myeloma received continuous infusions of vincristine (0.4 mg total dose daily for 4 days) and adriamycin (9 mg m-2 daily for 4 days) with a high dose of methylprednisolone (1 g m-2 i.v. or p.o. daily by 1 h infusion), the VAMP regimen [15].
• In conclusion, our findings exhibit the presence of two different populations of acceptors for tetanus toxin in central and peripheral nervous system and show that synaptobrevin cleavage may account for intracellular toxicity in Torpedo [16].

Biological context of VAMP1

• Mutational analysis of VAMP domains implicated in Ca2+-induced insulin exocytosis [17].
• In the presence of TeNT, exocytosis was restored by transfection of TeNT-resistant (Q(76)V, F(77)W) VAMP, but additional targeted mutations in VAMP(77-90) abolished its ability to rescue release [18].
• By employing deletion mutagenesis we found that deletion of the amino-terminal 18 amino acids of SNAP-23 (encoded in the first exon) dramatically inhibited binding of SNAP-23 to both the target SNARE syntaxin and the vesicle SNARE vesicle-associated membrane protein(VAMP) [19].
• The coding regions of the synaptobrevin genes are highly homologous to each other and are interrupted at identical positions by introns of different size and sequence [20].
• Tetanus toxin and the seven serologically distinct botulinal neurotoxins (BoNT/A to BoNT/G) abrogate synaptic transmission at nerve endings through the action of their light chains (L chains), which proteolytically cleave VAMP (vesicle-associated membrane protein)/synaptobrevin, SNAP-25 (synaptosome-associated protein of 25 kDa), or syntaxin [21].

Anatomical context of VAMP1

• Comparisons of the synaptobrevin sequences in five species from Drosophila with man indicate a selective conservation of sequences adjacent to the synaptic vesicle surface, suggesting a function at the membrane-cystosol interface [20].
• These findings support the involvement of SNAP-25 in the invertebrate sperm acrosome reaction, possibly through increased association with VAMP and syntaxin driving the fusion of plasma and acrosomal membranes [22].
• We have examined the role of the R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) synaptobrevin-2/vesicle-associated membrane protein (VAMP)-2 in neutrophil exocytosis [23].
• Expression of human SNAP-23 in a rat mast cell line significantly enhanced exocytosis, and this effect was not observed in transfectants expressing the carboxyl-terminal VAMP-binding mutant of SNAP-23 [19].
• Two isoforms for each of these proteins, syntaxins 1A and 1B and synaptobrevin/VAMPs 1 and 2, have been found in nerve endings [24].

Associations of VAMP1 with chemical compounds

• A substrate analogue with valine in the P1 position corresponding to the sequence of rat VAMP-1 was not cleaved [2].
• The ability of VAMP to capture protein-free (3)H-labeled trans liposomes was then measured [25].
• Calcium-triggered exocytosis of histamine is mediated by interacting SNARE proteins, especially by synaptobrevin and SNAP-25 [26].
• VAMP is phosphorylated by calcium/calmodulin-dependent protein kinase II on serine 61. alpha SNAP is phosphorylated by PKA; however, the beta SNAP isoform is phosphorylated only 20% as efficiently. alpha SNAP phosphorylated by PKA binds to the core docking and fusion complex 10 times weaker than the dephosphorylated form [27].
• Surface plasmon resonance and pull-down assays revealed Ca(2+)-dependent calmodulin binding (K(d) = 500 nM) to glutathione S-transferase fusion proteins containing synaptobrevin (VAMP 2) domains but not to syntaxin 1 or synaptosomal-associated protein of 25 kDa (SNAP-25) [28].

Physical interactions of VAMP1

• VAP-A has been implicated in vesicle targeting to the plasma membrane based on its location in polarized cells and its ability to bind VAMP in vitro [29].
• This reaction leads to the previously described disassembly of the fusion complex, since synaptobrevin binding to syntaxin is also reduced. alpha-SNAP binds to a carboxyl-terminal syntaxin fragment (residues 194-288) that also binds synaptobrevin and SNAP-25 [30].
• However, NSF action on this syntaxin fragment has no effect on the binding of alpha-SNAP or synaptobrevin [30].
• We found that the synaptosome-associated protein (SNAP-25) and the vesicle-associated membrane proteins (VAMP) coimmunoprecipitate with hTRPC1 in platelets [31].

Other interactions of VAMP1

• Transient transfection of HIT-T15 cells with VAMP-1, VAMP-2 or cellubrevin made resistant to the proteolytic action of TeTx by amino acid replacements in the cleavage site restored Ca2+-stimulated secretion [17].
• Assembly of a ternary complex by the predicted minimal coiled-coil-forming domains of syntaxin, SNAP-25, and synaptobrevin. A circular dichroism study [32].
• We report the identification of a human homologue of the vesicle-associated membrane protein (VAMP)-associated protein (hVAP-33) that has been implicated in neuronal exocytosis in Aplysia californica [33].
• Previous studies indicated that the v-SNARE, vesicle-associated membrane protein (VAMP)-2, as well as t-SNAREs (SNAP-23, syntaxin-4 and -6) are implicated in exocytosis from human granulocytes [34].
• Results: Vesicle-associated membrane proteins-7 and -8 were localized to granule and membrane-enriched fractions in eosinophils and neutrophils, whereas syntaxin-6 was not detectable [34].

Analytical, diagnostic and therapeutic context of VAMP1

• A complex containing SNAP-25, syntaxin, and VAMP is present in sperm, as detected by affinity chromatography and immunoprecipitation [22].
• Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins [35].
• To evaluate cis lipid binding, recombinant VAMP was reconstituted into liposomes and accessibility to site-directed antibodies was probed by surface plasmon resonance [25].
• Subsequent immunoblotting of single-cell pairs demonstrated directly that the tetanus toxin-mediated block of exocytosis is accompanied by cleavage of synaptobrevin in the injected neuron, resulting in the generation of a detectable C-terminal cleavage product [36].
• VAMP was found associated with synaptic vesicles, as also shown by conventional electron microscopy immunolabeling, and to the presynaptic plasma membrane (P leaflet) [37].

References