Alternative titles; symbols
HGNC Approved Gene Symbol: VAMP8
Cytogenetic location: 2p11.2 Genomic coordinates (GRCh38) : 2:85,577,586-85,582,031 (from NCBI)
Synaptobrevins/VAMPs, syntaxins (e.g., 186590), and the 25-kD synaptosomal-associated protein SNAP25 (600322) are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. Bock and Scheller (1997) reviewed the 'SNARE (SNAP receptor) hypothesis' of vesicular trafficking.
By searching sequence databases with the sequences of VAMP family members, Wong et al. (1998) and Bock and Scheller (1997) identified mammalian ESTs encoding VAMP8, or endobrevin, a protein with sequence similarity to synaptobrevins. Wong et al. (1998) reported that the predicted 100-amino acid human protein shares approximately 32%, 33%, and 31% sequence identity with VAMP1 (185880), VAMP2 (185881), and cellubrevin (VAMP3; 603657), respectively. Endobrevin migrates as a 15-kD protein on Western blots of mammalian cell extracts. Membrane fractionation, immunofluorescence, and electron microscopy studies demonstrated that endobrevin is associated with the perinuclear vesicular structures of the early endocytic compartment.
Advani et al. (1998) cloned Vamp8 from an embryonic mouse cDNA library. The deduced 101-amino acid protein contains an amphipathic helix that may participate in coiled-coil interactions and a C-terminal hydrophobic domain predicted to serve as a membrane anchor. Northern blot analysis of mouse tissues revealed abundant expression in kidney, intermediate expression in heart and spleen, and lower expression in brain, thymus, and liver. Transfection of Vamp8 into normal rat kidney cells resulted in broadly distributed puncta throughout the cell with a juxtanuclear enrichment.
Using in vitro binding assays, Wong et al. (1998) found that endobrevin interacts specifically with the soluble NSF (601633)-attachment protein (NAPA; 603215), most likely through an endobrevin-containing SNARE complex.
Low et al. (2003) found that 2 members of the SNARE membrane fusion machinery, syntaxin-2 (EPIM; 132350) and Vamp8, localized to the midbody during cytokinesis in rat and canine kidney cell lines. Inhibition of syntaxin-2 and Vamp8 function by overexpression of nonmembrane-anchored mutants caused failure of cytokinesis leading to the formation of binucleated cells. Time-lapse microscopy showed that only midbody abscission and not further upstream events, such as furrowing, were affected.
Using RT-PCR, immunoblot analysis, and immunofluorescence microscopy, Sander et al. (2008) demonstrated that human intestinal mast cells (MCs) expressed SNAP23 (602534), STX1B (601485), STX2, STX3 (STX3A; 600876), STX4 (STX4A; 186591), and STX6 (603944), but not SNAP25. MCs also expressed VAMP3, VAMP7 (300053), and VAMP8, but, in contrast with rodent MCs, they expressed only low levels of VAMP2. VAMP7 and VAMP8 translocated to the plasma membrane and interacted with SNAP23 and STX4 upon activation. Inhibition of STX4, SNAP23, VAMP7, or VAMP8, but not VAMP2 or VAMP3, resulted in markedly reduced high-affinity IgE receptor-mediated histamine release. Sander et al. (2008) concluded that human MCs express a specific pattern of SNAREs and that VAMP7 and VAMP8, but not VAMP2, are required for rapid degranulation.
By radiation hybrid analysis, Bui et al. (1998) mapped the VAMP8 gene to human chromosome 2p12-p11.2 and to a region of conserved synteny on mouse chromosome 6.
Wang et al. (2004) found that Vamp8-null mice developed normally but showed severe defects in the pancreas. Mutant acinar cells contained 3 times more zymogen granules than control acinar cells. Furthermore, secretagogue-stimulated secretion was abolished in pancreatic fragments derived from Vamp8-null mice. Mutant mice were partially resistant to supramaximal cerulein-induced pancreatitis. Characterization of Vamp8 expression indicated that the protein was enriched on the membrane of zymogen granules and existed in a complex with syntaxin-4 and Snap23. Wang et al. (2004) concluded that VAMP8 plays a major role in regulating exocytosis in pancreatic acinar cells by serving as a v-SNARE of zymogen granules.
Pushparaj et al. (2009) reported studies in Vamp8 -/- mice suggesting that VAMP8 is required for correct trafficking of secretory lysosomal granules for exocytosis in macrophages and for the release of TNF. Pushparaj and Tay (2013) retracted this paper because of the finding of plagiarism and 'serious scientific misconduct' by one of the authors, Dr. Melendez.
Advani, R. J., Bae, H.-R., Bock, J. B., Chao, D. S., Doung, Y.-C., Prekeris, R., Yoo, J.-S., Scheller, R. H. Seven novel mammalian SNARE proteins localize to distinct membrane compartments. J. Biol. Chem. 273: 10317-10324, 1998. [PubMed: 9553086] [Full Text: https://doi.org/10.1074/jbc.273.17.10317]
Bock, J. B., Scheller, R. H. A fusion of new ideas. Nature 387: 133-135, 1997. [PubMed: 9144278] [Full Text: https://doi.org/10.1038/387133a0]
Bui, T. D., Wong, S. H., Lu, L., Hong, W. Endobrevin maps to chromosome 2 in human and chromosome 6 in mouse. Genomics 54: 579-580, 1998. [PubMed: 9878266] [Full Text: https://doi.org/10.1006/geno.1998.5596]
Low, S. H., Li, X., Miura, M., Kudo, N., Quinones, B., Weimbs, T. Syntaxin 2 and endobrevin are required for the terminal step of cytokinesis in mammalian cells. Dev. Cell 4: 753-759, 2003. [PubMed: 12737809] [Full Text: https://doi.org/10.1016/s1534-5807(03)00122-9]
Pushparaj, P. N., Tay, H. K. Retraction: VAMP8 is essential in anaphylatoxin-induced deregulation, TNF-alpha secretion, peritonitis, and systemic inflammation. J. Immun. 190: 3007 only, 2013. [PubMed: 23456703] [Full Text: https://doi.org/10.4049/jimmunol.1390008]
Pushparaj, P. N., Tay, H. K., Wang, C.-C., Hong, W., Melendez, A. J. VAMP8 is essential in anaphylatoxin-induced degranulation, TNF-alpha secretion, peritonitis, and systemic inflammation. J. Immun. 183: 1413-1418, 2009. Note: Retraction: J. Immun. 190: 3007 only, 2013. [PubMed: 19564343] [Full Text: https://doi.org/10.4049/jimmunol.0804061]
Sander, L. E., Frank, S. P. C., Bolat, S., Blank, U., Galli, T., Bigalke, H., Bischoff, S. C., Lorentz, A. 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. Europ. J. Immun. 38: 855-863, 2008. [PubMed: 18253931] [Full Text: https://doi.org/10.1002/eji.200737634]
Wang, C.-C., Ng, C. P., Lu, L., Atlashkin, V., Zhang, W., Seet, L.-F., Hong, W. A role of VAMP8/endobrevin in regulated exocytosis of pancreatic acinar cells. Dev. Cell 7: 359-371, 2004. [PubMed: 15363411] [Full Text: https://doi.org/10.1016/j.devcel.2004.08.002]
Wong, S. H., Zhang, T., Xu, Y., Subramaniam, V. N., Griffiths, G., Hong, W. Endobrevin, a novel synaptobrevin/VAMP-like protein preferentially associated with the early endosome. Molec. Biol. Cell 9: 1549-1563, 1998. [PubMed: 9614193] [Full Text: https://doi.org/10.1091/mbc.9.6.1549]