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Vesicle fusion is the process of a vesicle approaching a membrane (or another vesicle) and then fusing with it. The SNARE complex, a four-domain complex, is involved in bringing the vesicle in contact with the membrane and bringing about the exocytotic event. Synaptobrevin(VAMP) is bound to the vesicle and contributes one α-helix to the complex while SNAP-25[1] , a Q-SNARE protein, contributes two helices and Syntaxin-1 contributes one helix, both being bound to the plasma membrane. SNAP-25 is a membrane-bound protein anchored to the cytosolic face of membranes via palmitoyl side chains covalently bound to cysteine amino acid residues in the middle of the molecule. This means that SNAP-25 does not contain a trans-membrane domain[2]. SNAP-25 assembles with the other two SNARE complex proteins and the selective binding of these proteins enables vesicle docking and fusion to occur at the correct location[3].
To form the SNARE complex, the SNARE attached to the vesicle membrane and the two SNARES attached to the plasma membrane associated with each other and begin to wrap around each other and form a coiled coil quarternary structure. The SNARE domains of both synaptobrevin and syntaxin bind to SNAP-25 [4]. The two proteins bind to one each of the different SNARE regions on the SNAP-25 protein. Syntaxin binds the α-helix near SNAP-25's N-terminus side[5] while Synaptobrevin binds the c-terminal α-helix.
SNAP-25 inhibits P/Q- and L-type voltage-gated calcium channels located presynaptically[6] and interacts with the synaptotagmin C2B domain in Ca2+-independent fashion.[7] In glutamatergic synapses SNAP-25 decreases the Ca2+ responsiveness, while it is naturally absent in GABAergic synapses.[8]
Two isoforms (mRNA splice variants) of SNAP-25 exist, which are labeled a and b. There are nine amino acid residue differences between the isoforms, including a re-localization of on of the four cysteine residues.[9]. The major characteristics of these two forms are outlined in the table below.
| SNAP25A | SNAP25B | |
|---|---|---|
| Structure | N-terminal α-helix
random coil linker region with four cysteines clustered towards the center C-terminal α-helix |
N-terminal α-helix
random coil linker region with four cysteines clustered towards the C-terminus C-terminal α-helix |
| Expression | Major SNAP-25 isoform in embryos and developing neural tissue.
Minimal expression in adult tissue except in pituitary and adrenal gland tissues. |
Minimal expression during development, major isoform in adult neural tissue.[10] |
| Localization | Diffuse | Localized to terminals and varicosities[11] |
- ^ Pevsner, Jonathan; Hsu, Shu-Chan; Braun, Janice E. A.; Calakos, Nicole; Ting, Anthony E.; Bennett, Mark K.; Scheller, Richard H. (August 1994). "Specificity and regulation of a synaptic vesicle docking complex". Neuron. 13 (2): 353-361. doi:10.1016/0896-6273994090352-2.
{{cite journal}}:|access-date=requires|url=(help) - ^ Chapman, E. R; An, S.; Barton, N.; Jahn, R. (1994). "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.
{{cite journal}}:|access-date=requires|url=(help) - ^ Calakos, N.; Bennett, M.; Peterson, K.C.; Scheller, R.H (1994). "Protein-protein interactions contributing to the specificity of intracellular vesicular trafficking". Science. 263: 1146-1149.
{{cite journal}}:|access-date=requires|url=(help) - ^ Chapman, E. R; An, S.; Barton, N.; Jahn, R. (1994). "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.
{{cite journal}}:|access-date=requires|url=(help) - ^ Chapman, E. R; An, S.; Barton, N.; Jahn, R. (1994). "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.
{{cite journal}}:|access-date=requires|url=(help) - ^ Hodel A (October 1998). "SNAP-25". Int. J. Biochem. Cell Biol. 30 (10): 1069–73. doi:10.1016/S1357-2725(98)00079-X. PMID 9785471.
- ^ Chapman ER (July 2002). "Synaptotagmin: a Ca(2+) sensor that triggers exocytosis?" (PDF). Nat. Rev. Mol. Cell Biol. 3 (7): 498–508. doi:10.1038/nrm855. PMID 12094216. [dead link]
- ^ Verderio C, Pozzi D, Pravettoni E, Inverardi F, Schenk U, Coco S, Proux-Gillardeaux V, Galli T, Rossetto O, Frassoni C, Matteoli M (February 2004). "SNAP-25 modulation of calcium dynamics underlies differences in GABAergic and glutamatergic responsiveness to depolarization". Neuron. 41 (4): 599–610. doi:10.1016/S0896-6273(04)00077-7. PMID 14980208.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Nagy, Gabor (Dec 2005). "Alternative Splicing of SNAP-25 Regulates Secretion through Nonconservative Substitutions in the SNARE Domain". Molecular Biology of the Cell. 16 (12): 5675–5685. doi:10.1091/mbc.E05-07-0595. PMID PMC1289412. Retrieved 18 October 2014.
{{cite journal}}: Check|pmid=value (help) - ^ Bark, Christina (February 1995). "Differential expression of SNAP-25 protein isoforms during divergent vesicle fusion events of neural development". Proceedings of the Nation Academies of Sciences. 92 (5): 1510–1514. doi:10.1073/pnas.92.5.1510. Retrieved 18 October 2014.
- ^ Bark, Christina (February 1995). "Differential expression of SNAP-25 protein isoforms during divergent vesicle fusion events of neural development". Proceedings of the Nation Academies of Sciences. 92 (5): 1510–1514. doi:10.1073/pnas.92.5.1510. Retrieved 18 October 2014.