Disease relevance of Vamp3

• Like synaptobrevin II, cellubrevin is proteolysed by tetanus toxin light chain in vitro and after transfection [1].

High impact information on Vamp3

• Cellubrevin, a nonneural VAMP homolog, contains this signal and is also targeted to synaptic vesicles [2].
• Cellubrevin is a ubiquitous tetanus-toxin substrate homologous to a putative synaptic vesicle fusion protein [1].
• Here we describe a new synaptobrevin homologue, cellubrevin, that is present in all cells and tissues tested and demonstrate that it is a membrane trafficking protein of a constitutively recycling pathway [1].
• Using postembedding immunogold labeling of the rat hippocampus, we show that vesicular glutamate transporters (VGLUT1/2) and the vesicular SNARE protein, cellubrevin, are both expressed in small vesicular organelles that resemble synaptic vesicles of glutamatergic terminals [3].
• Below the membrane, GLUT4 and the vesicular protein VAMP2, but not VAMP3, colocalized with the actin structures supporting the membrane ruffles [4].

Chemical compound and disease context of Vamp3

• In this study we show that proteolysis of both cellubrevin and VAMP, induced by electroporation of isolated rat adipocytes with tetanus toxin, does not impair insulin-stimulated glucose transport or GLUT4 translocation [5].

Biological context of Vamp3

• These results suggest that cellubrevin and the synaptobrevins have similar function and do not play a specialized role in constitutive and regulated exocytosis, respectively [6].
• Cellubrevin, a very similar protein, has a widespread tissue distribution and in fibroblasts is localized on endosome-derived, transferin receptor-positive vesicles [6].
• Pretreatment of streptolysin-O permeabilized insulin-secreting cells with tetanus and botulinum B neurotoxins selectively cleaved VAMP-2 and cellubrevin and abolished Ca(2+)-induced insulin release (IC50 approximately 15 nM) [7].
• These data suggest that the t-SNAREs SNAP-23 and syntaxin 1 and the v-SNARE cellubrevin participate in general membrane insertion mechanisms involved in diverse glial cell functions such as secretion, phagocytosis, and myelinogenesis [8].
• Botulinum toxins also exploit endocytosis to enter cultured astrocytes, where they partially cleave cellubrevin, a ubiquitous synaptobrevin/VAMP isoform [9].

Anatomical context of Vamp3

• Cellubrevin and synaptobrevins: similar subcellular localization and biochemical properties in PC12 cells [6].
• However, cellubrevin is coexpressed with the two synaptobrevins in PC12 cells, a neuroendocrine cell line which contains synaptic vesicle-like microvesicles [6].
• RESULTS: Both VAMP-2 and cellubrevin were present on both the zymogen granule membrane and plasma membrane [10].
• We suggest that the cytotoxic effects of LF-LC result from inhibition of a specific intracellular membrane fusion event mediated by cellubrevin [11].
• Expression of vesicle-associated membrane protein 2 (VAMP-2)/synaptobrevin II and cellubrevin in rat skeletal muscle and in a muscle cell line [12].

Associations of Vamp3 with chemical compounds

• After subcellular fractionation on continuous sucrose gradients, VAMP-2 and cellubrevin were found to be associated with both types of secretory vesicle [7].
• VAMP-2 and cellubrevin are expressed in pancreatic beta-cells and are essential for Ca(2+)-but not for GTP gamma S-induced insulin secretion [7].
• On the other hand, nocodazole partially inhibited insulin-induced translocation of the insulin-regulated aminopeptidase and the vesicle-associated membrane protein (VAMP)-2 without affecting GLUT1 and VAMP-3 [13].
• The lack of any significant change in insulin-stimulated glucose transport was consistent with the finding that toxin-mediated proteolysis of both cellubrevin and VAMP had no detectable effect on insulin-induced translocation of GLUT4 in adipocytes [5].
• In striking contrast, the levels of all of these exocytotic proteins, including cellubrevin, were notably decreased in pituitary glands of E2-treated rats [14].

Physical interactions of Vamp3

• Interestingly, only in those isolated endosomal fractions, endosomes enriched in transcytotic structures (of livers loaded with IgA), the polymeric immunoglobulin receptor specifically co-immunoprecipitated with cellubrevin [15].

Other interactions of Vamp3

• In PC12 cells, cellubrevin has a distribution very similar to that of synaptobrevin 1 and 2 [6].
• Moreover, both cellubrevin and synaptobrevin 2 took part of a protein complex involved in the fusion process in adenohypophyseal cells [16].
• Finally, cellubrevin, like the synaptobrevins, interact with the neuronal t-SNAREs syntaxin 1 and SNAP-25 [6].
• Coupled to the recent detection of vesicle associated membrane protein-2 and cellubrevin in skeletal muscle, syntaxin 4 may play a role in membrane traffic in this tissue [17].
• Recombinant synaptobrevin I bound with similar efficiency, whereas the non-neuronal isoform cellubrevin displayed a lower affinity towards synaptophysin [18].

Analytical, diagnostic and therapeutic context of Vamp3

• Western blot analysis with a polyclonal antibody against the unique N-terminus of cellubrevin identified a protein of 14 kDa in rat pancreas [19].
• Light and electron microscopic immunocytochemistry localized cellubrevin immunoreactivity primarily to small vesicles and condensing vacuoles originating from the Golgi region, with significantly lower labeling on zymogen granules [19].
• Electroporation of adipocytes with 600 nM tetanus toxin resulted in a complete loss of both cellubrevin and VAMP expression within 60 min [5].
• We now show by immunogold electron microscopy that cellubrevin is present on vesicles containing water channels, that it is associated with both coated and uncoated vesicles, and that it is present on the apical membrane [20].
• In a yeast two-hybrid assay, syntaxins 2, 3 and 4 interacted with SNAP-23 and VAMP-3 [21].

References