VAMP2 explained

Vesicle-associated membrane protein 2 (VAMP2) is a protein that in humans is encoded by the VAMP2 gene.^{[1] [2]}

Function

Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. VAMP2 is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. VAMP2 is thought to participate in neurotransmitter release at a step between docking and fusion. Mice lacking functional synaptobrevin2/VAMP2 gene cannot survive after birth, and have a dramatically reduced synaptic transmission, around 10% of control.^[3] The protein forms a stable complex with syntaxin, synaptosomal-associated protein, 25 kD, and complexin. It also forms a distinct complex with synaptophysin.

Clinical significance

Heterozygous mutations in VAMP2 cause a neurodevelopmental disorder with hypotonia and autistic features (with or without hyperkinetic movements).^{[4] [5] [6]}

Interactions

VAMP2 has been shown to interact with:

• RABAC1,^[7]
• SNAP-25,^{[8] [9] [10]}
• SNAP23,^{[11] [12]}
• STX1A,^{[9] [10] [13] [14] [15] [16]} and
• STX4.^{[17] [18] [19] [20]}

Further reading

• Brumell JH, Volchuk A, Sengelov H, Borregaard N, Cieutat AM, Bainton DF, Grinstein S, Klip A . Subcellular distribution of docking/fusion proteins in neutrophils, secretory cells with multiple exocytic compartments . Journal of Immunology . 155 . 12 . 5750–9 . Dec 1995 . 10.4049/jimmunol.155.12.5750 . 7499863 . 32809167 .
• Kutay U, Ahnert-Hilger G, Hartmann E, Wiedenmann B, Rapoport TA . Transport route for synaptobrevin via a novel pathway of insertion into the endoplasmic reticulum membrane . The EMBO Journal . 14 . 2 . 217–23 . Jan 1995 . 7835332 . 398073 . 10.1002/j.1460-2075.1995.tb06994.x.
• Chapman ER, An S, Barton N, Jahn R . SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils . The Journal of Biological Chemistry . 269 . 44 . 27427–32 . Nov 1994 . 10.1016/S0021-9258(18)47003-2 . 7961655 . free .
• Hunt JM, Bommert K, Charlton MP, Kistner A, Habermann E, Augustine GJ, Betz H . A post-docking role for synaptobrevin in synaptic vesicle fusion . Neuron . 12 . 6 . 1269–79 . Jun 1994 . 8011337 . 10.1016/0896-6273(94)90443-X . 799315 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Jagadish MN, Fernandez CS, Hewish DR, Macaulay SL, Gough KH, Grusovin J, Verkuylen A, Cosgrove L, Alafaci A, Frenkel MJ, Ward CW . Insulin-responsive tissues contain the core complex protein SNAP-25 (synaptosomal-associated protein 25) A and B isoforms in addition to syntaxin 4 and synaptobrevins 1 and 2 . The Biochemical Journal . 317 . 3. 945–54 . Aug 1996 . 8760387 . 1217577 . 10.1042/bj3170945. 317 .
• Mandon B, Chou CL, Nielsen S, Knepper MA . Syntaxin-4 is localized to the apical plasma membrane of rat renal collecting duct cells: possible role in aquaporin-2 trafficking . The Journal of Clinical Investigation . 98 . 4 . 906–13 . Aug 1996 . 8770861 . 507504 . 10.1172/JCI118873 .
• Timmers KI, Clark AE, Omatsu-Kanbe M, Whiteheart SW, Bennett MK, Holman GD, Cushman SW . Identification of SNAP receptors in rat adipose cell membrane fractions and in SNARE complexes co-immunoprecipitated with epitope-tagged N-ethylmaleimide-sensitive fusion protein . The Biochemical Journal . 320 . 2. 429–36 . Dec 1996 . 8973549 . 1217948 . 10.1042/bj3200429. 320 .
• Betz A, Okamoto M, Benseler F, Brose N . Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin . The Journal of Biological Chemistry . 272 . 4 . 2520–6 . Jan 1997 . 8999968 . 10.1074/jbc.272.4.2520 . free .
• Hao JC, Salem N, Peng XR, Kelly RB, Bennett MK . Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes . The Journal of Neuroscience . 17 . 5 . 1596–603 . Mar 1997 . 9030619 . 10.1523/JNEUROSCI.17-05-01596.1997 . 6573372.
• Martincic I, Peralta ME, Ngsee JK . Isolation and characterization of a dual prenylated Rab and VAMP2 receptor . The Journal of Biological Chemistry . 272 . 43 . 26991–8 . Oct 1997 . 9341137 . 10.1074/jbc.272.43.26991 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Weir ML, Klip A, Trimble WS . Identification of a human homologue of the vesicle-associated membrane protein (VAMP)-associated protein of 33 kDa (VAP-33): a broadly expressed protein that binds to VAMP . The Biochemical Journal . 333 . 2. 247–51 . Jul 1998 . 9657962 . 1219579 . 10.1042/bj3330247. 333 .
• Isenmann S, Khew-Goodall Y, Gamble J, Vadas M, Wattenberg BW . A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal . Molecular Biology of the Cell . 9 . 7 . 1649–60 . Jul 1998 . 9658161 . 25402 . 10.1091/mbc.9.7.1649 .
• Prekeris R, Klumperman J, Chen YA, Scheller RH . Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes . The Journal of Cell Biology . 143 . 4 . 957–71 . Nov 1998 . 9817754 . 2132958 . 10.1083/jcb.143.4.957 .
• Nishimura Y, Hayashi M, Inada H, Tanaka T . Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins . Biochemical and Biophysical Research Communications . 254 . 1 . 21–6 . Jan 1999 . 9920726 . 10.1006/bbrc.1998.9876 .
• Valdez AC, Cabaniols JP, Brown MJ, Roche PA . Syntaxin 11 is associated with SNAP-23 on late endosomes and the trans-Golgi network . Journal of Cell Science . 112 . 6. 845–54 . Mar 1999 . 10036234 . 112 . 10.1242/jcs.112.6.845 .
• Margittai M, Otto H, Jahn R . A stable interaction between syntaxin 1a and synaptobrevin 2 mediated by their transmembrane domains . FEBS Letters . 446 . 1 . 40–4 . Mar 1999 . 10100611 . 10.1016/S0014-5793(99)00028-9 . 9115709 . free .
• Fasshauer D, Antonin W, Margittai M, Pabst S, Jahn R . Mixed and non-cognate SNARE complexes. Characterization of assembly and biophysical properties . The Journal of Biological Chemistry . 274 . 22 . 15440–6 . May 1999 . 10336434 . 10.1074/jbc.274.22.15440 . free .

Notes and References

1. Archer BT, Ozçelik T, Jahn R, Francke U, Südhof TC . Structures and chromosomal localizations of two human genes encoding synaptobrevins 1 and 2 . The Journal of Biological Chemistry . 265 . 28 . 17267–73 . Oct 1990 . 10.1016/S0021-9258(17)44898-8 . 1976629 . free .
2. Web site: Entrez Gene: VAMP2 vesicle-associated membrane protein 2 (synaptobrevin 2).
3. Schoch S, Deák F, Königstorfer A, Mozhayeva M, Sara Y, Südhof TC, Kavalali ET . SNARE function analyzed in synaptobrevin/VAMP knockout mice . Science . 294 . 5544 . 1117–22 . Nov 2001 . 11691998 . 10.1126/science.1064335 . 2001Sci...294.1117S . 40321111 .
4. Salpietro V, Malintan NT, Llano-Rivas I, et al. . Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment . The American Journal of Human Genetics . 104 . 4 . 721–730 . Apr 2019 . 30929742 . 10.1016/j.ajhg.2019.02.016. 6451933 . free .
5. Sunaga Y, Muramatsu K, Kosaki K, et al. . Variant in the neuronal vesicular SNARE VAMP2 (synaptobrevin-2): First report in Japan . Brain and Development . Apr 2020 . 42 . 7 . 529–533 . 32336483 . 10.1016/j.braindev.2020.04.001 . 216095891 .
6. Web site: OMIM entry: Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements.
7. Martincic I, Peralta ME, Ngsee JK . Isolation and characterization of a dual prenylated Rab and VAMP2 receptor . The Journal of Biological Chemistry . 272 . 43 . 26991–8 . Oct 1997 . 9341137 . 10.1074/jbc.272.43.26991. free .
8. Li Y, Chin LS, Weigel C, Li L . Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis . The Journal of Biological Chemistry . 276 . 44 . 40824–33 . Nov 2001 . 11524423 . 10.1074/jbc.M106141200 . free .
9. Hao JC, Salem N, Peng XR, Kelly RB, Bennett MK . Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes . The Journal of Neuroscience . 17 . 5 . 1596–603 . Mar 1997 . 9030619 . 10.1523/JNEUROSCI.17-05-01596.1997 . 6573372.
10. Chen X, Tomchick DR, Kovrigin E, Araç D, Machius M, Südhof TC, Rizo J . Three-dimensional structure of the complexin/SNARE complex . Neuron . 33 . 3 . 397–409 . Jan 2002 . 11832227 . 10.1016/s0896-6273(02)00583-4. 17878965 . free .
11. Imai A, Nashida T, Yoshie S, Shimomura H . Intracellular localisation of SNARE proteins in rat parotid acinar cells: SNARE complexes on the apical plasma membrane . Archives of Oral Biology . 48 . 8 . 597–604 . Aug 2003 . 12828989 . 10.1016/s0003-9969(03)00116-x.
12. Kawanishi M, Tamori Y, Okazawa H, Araki S, Shinoda H, Kasuga M . Role of SNAP23 in insulin-induced translocation of GLUT4 in 3T3-L1 adipocytes. Mediation of complex formation between syntaxin4 and VAMP2 . The Journal of Biological Chemistry . 275 . 11 . 8240–7 . Mar 2000 . 10713150 . 10.1074/jbc.275.11.8240. free .
13. Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J . A conformational switch in syntaxin during exocytosis: role of munc18 . The EMBO Journal . 18 . 16 . 4372–82 . Aug 1999 . 10449403 . 1171512 . 10.1093/emboj/18.16.4372 .
14. McMahon HT, Missler M, Li C, Südhof TC . Complexins: cytosolic proteins that regulate SNAP receptor function . Cell . 83 . 1 . 111–9 . Oct 1995 . 7553862 . 10.1016/0092-8674(95)90239-2. 675343 . free .
15. Pérez-Brangulí F, Muhaisen A, Blasi J . Munc 18a binding to syntaxin 1A and 1B isoforms defines its localization at the plasma membrane and blocks SNARE assembly in a three-hybrid system assay . Molecular and Cellular Neurosciences . 20 . 2 . 169–80 . Jun 2002 . 12093152 . 10.1006/mcne.2002.1122. 23927545 .
16. Margittai M, Otto H, Jahn R . A stable interaction between syntaxin 1a and synaptobrevin 2 mediated by their transmembrane domains . FEBS Letters . 446 . 1 . 40–4 . Mar 1999 . 10100611 . 10.1016/s0014-5793(99)00028-9. 9115709 . free .
17. Paumet F, Le Mao J, Martin S, Galli T, David B, Blank U, Roa M . Soluble NSF attachment protein receptors (SNAREs) in RBL-2H3 mast cells: functional role of syntaxin 4 in exocytosis and identification of a vesicle-associated membrane protein 8-containing secretory compartment . Journal of Immunology . 164 . 11 . 5850–7 . Jun 2000 . 10820264 . 10.4049/jimmunol.164.11.5850. free .
18. Mollinedo F, Martín-Martín B, Calafat J, Nabokina SM, Lazo PA . Role of vesicle-associated membrane protein-2, through Q-soluble N-ethylmaleimide-sensitive factor attachment protein receptor/R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor interaction, in the exocytosis of specific and tertiary granules of human neutrophils . Journal of Immunology . 170 . 2 . 1034–42 . Jan 2003 . 12517971 . 10.4049/jimmunol.170.2.1034. free .
19. Jagadish MN, Fernandez CS, Hewish DR, Macaulay SL, Gough KH, Grusovin J, Verkuylen A, Cosgrove L, Alafaci A, Frenkel MJ, Ward CW . Insulin-responsive tissues contain the core complex protein SNAP-25 (synaptosomal-associated protein 25) A and B isoforms in addition to syntaxin 4 and synaptobrevins 1 and 2 . The Biochemical Journal . 317 . 3. 945–54 . Aug 1996 . 8760387 . 1217577 . 10.1042/bj3170945. 317 .
20. Reed GL, Houng AK, Fitzgerald ML . Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion . Blood . 93 . 8 . 2617–26 . Apr 1999 . 10194441 . 10.1182/blood.V93.8.2617.