Disease relevance of Vamp2

• Both cellubrevin and VAMP-2 were susceptible to cleavage by tetanus toxin [1].
• In the current study, we overexpressed syntaxin 1A, SNAP-25b, and VAMP-2 in PC12 cells using recombinant adenoviruses, and determined their effects on membrane trafficking involving neurite outgrowth [2].

High impact information on Vamp2

• We generated knockout mice lacking synaptobrevin/VAMP 2, the vesicular SNARE protein responsible for synaptic vesicle fusion in forebrain synapses, to make use of the exquisite temporal resolution of electrophysiology in measuring fusion [3].
• In the absence of synaptobrevin 2, spontaneous synaptic vesicle fusion and fusion induced by hypertonic sucrose were decreased approximately 10-fold, but fast Ca2+-triggered fusion was decreased more than 100-fold [3].
• MISTs consist of modified presynaptic proteins that interfere with the synaptic vesicle cycle when crosslinked by small molecule "dimerizers." MISTs based on the vesicle proteins VAMP2/Synaptobrevin and Synaptophysin induced rapid ( approximately 10 min) and reversible block of synaptic transmission in cultured neurons and brain slices [4].
• We find that synaptobrevin II and cellubrevin differentially control the pool of readily releasable vesicles and show that the v-SNARE's amino terminus regulates the vesicle's primed state [5].
• Immuno-EM on intracellular vesicles from adipocytes revealed that VAMP-2 was colocalized with GLUT-4, whereas only partial colocalization was observed between GLUT-4 and cellubrevin [6].

Chemical compound and disease context of Vamp2

• Finally, glutamate and AA were released solely from neurons as tetanus toxin did not cleave astrocytic synaptobrevin-2, nor was AA released from pure astrocyte cultures using the same stimuli that were effective in mixed cultures [7].

Biological context of Vamp2

• Synaptobrevin-2 (VAMP-2), the major SNARE protein of synaptic vesicles, is required for fast calcium-triggered synaptic-vesicle exocytosis [8].
• Here we show that synaptobrevin-2 is also essential for fast synaptic-vesicle endocytosis [8].
• Binary interactions of the SNARE proteins syntaxin-4, SNAP23, and VAMP-2 and their regulation by phosphorylation [9].
• More precise mapping using microsatellite markers revealed close linkage of the Hd locus with the D1OMit8 marker defining Syb2 gene coding for synaptobrevin 2 [10].

Anatomical context of Vamp2

• The glucose transporter (GLUT-4) and vesicle-associated membrane protein-2 (VAMP-2) are segregated from recycling endosomes in insulin-sensitive cells [6].
• In the OPL, VAMP-1 is co-expressed with VAMP-2 presynaptically in photoreceptor terminals [11].
• A direct interaction of GLUT4 storage vesicles with the plasma membrane has been implicated because the v-SNARE, vesicle-associated membrane protein-2 (VAMP2), appears to be a specific component of these vesicles [12].
• Both proteins associate with the cytoskeleton upon Ca(2+) store depletion, although only VAMP-2 seems to be sensitive to TeTx [13].
• Here, we show that each of the vesicle-associated SNARE proteins (v-SNARE) of a chromaffin granule, synaptobrevin II or cellubrevin, is sufficient to support Ca(2+)-dependent exocytosis and to establish a pool of primed, readily releasable vesicles [5].

Associations of Vamp2 with chemical compounds

• Membrane fractions were isolated from adipocytes and probed by far Western blotting with the cytosolic portion of VAMP2 fused to glutathione S-transferase [12].
• Using recombinant fragments of synaptobrevin-2 and synaptotagmin C2 domains we were able to dissociate the molecular requirements of vesicle exocytosis for initial membrane resealing and the facilitated and potentiated responses [14].
• To determine whether calcium-dependent glutamate release is mediated by exocytosis, we expressed the SNARE motif of synaptobrevin II to prevent the formation of SNARE complexes, which reduces glutamate release from astrocytes [15].
• Both cleavage of VAMP2/synaptobrevin2 and reduction of glutamate release were reversed by removal of DOX [16].
• In the present study we have used antisera directed against PLCbeta2, alpha-gustducin, serotonin (5-HT), PGP 9.5 and synaptobrevin-2 to determine the percentages of taste cells expressing these markers in taste buds in both rodent species [17].

Physical interactions of Vamp2

• Together, these data suggest that Munc18c inhibits the docking/fusion of GLUT4-containing vesicles by blocking the binding of VAMP2 to syntaxin 4 [18].

Regulatory relationships of Vamp2

• Insulin stimulation had no effect on the plasma membrane raft association of SNAP-23 or syntaxin 4 but promoted VAMP2 insertion into plasma membrane rafts [19].

Other interactions of Vamp2

• VAMP-1, VAMP-2, and cellubrevin cDNAs were isolated from a 3T3-L1 adipocyte expression library [6].
• These data taken together strongly suggest a role for VAMP 2 in GLUT4 trafficking and also for syntaxin 4 [20].
• Cleavage of SNAP-25 and VAMP-2 impairs store-operated Ca2+ entry in mouse pancreatic acinar cells [13].
• Our results show that GLUT4 overexpression or deficiency affects the amount of other GLUT4-vesicle proteins including IRAP and VAMP2 and that GLUT4 sequestration is saturable [21].
• In the current study, we used quantitative in situ hybridisation to examine mRNA expression of SNAREs (25 kDa synaptosome-associated protein (SNAP-25), syntaxin-1A and synaptobrevin-2) and SNARE-associated proteins (alpha-SNAP, CPLXI and CPLXII) in brain of R6/2 mice and their wild type littermates between 3 and 15 weeks of age [22].

Analytical, diagnostic and therapeutic context of Vamp2

• METHODS: Single- and double-labeling immunocytochemistry was used to investigate the distribution of the synaptic VAMP isoforms, VAMP-1 and VAMP-2, in the mouse retina [11].
• Microinjection of an N-terminal VAMP 2 peptide (residues 1-26) inhibited insulin stimulation of GLUT4 translocation by 54% [20].
• Using a yeast two-hybrid assay we demonstrate that the VAMP-2-like domain in Tomosyn facilitates the interaction with Syntaxin4 [23].
• Immunoblotting and RT-PCR showed that SNAP-25 levels are increased in the adrenal gland, but not in cerebellum, in knock-out mice, while syntaxin-1 and VAMP-2 are unaffected in either tissue [24].
• Western blotting and flow cytometric analysis were carried out to confirm the identity of VAMP-2 and its susceptibility to cleavage by tetanus toxin [25].

References