Structure and Function
edit| SNAP-25 family | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 Structure of a SNARE complex involved in synaptic exocytosis. | |||||||||||
| Identifiers | |||||||||||
| Symbol | SNAP-25 | ||||||||||
| Pfam | PF00835 | ||||||||||
| InterPro | IPR000928 | ||||||||||
| SCOP2 | 1sfc / SCOPe / SUPFAM | ||||||||||
| |||||||||||
SNAP-25, a Q-SNARE protein, is 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.[1]
SNAP-25 has been identified in contributing two α-helices to the SNARE complex, a four-α-helix domain complex.[2] The SNARE complex participates in vesicle fusion, which involves the docking and merging of a vesicle with the cell membrane to bring about an exocytotic event. Synaptobrevin, a protein that is part of the vesicle-associated membrane protein (VAMP) family, and syntaxin-1 also help form the SNARE complex by each contributing one α-helix. SNAP-25 assembles with synaptobrevin and syntaxin-1 and the selective binding of these proteins enables vesicle docking and fusion to occur at the correct location.[3]
To form the SNARE complex, synaptobrevin, syntaxin-1, and SNAP-25 associate and begin to wrap around each other to form a coiled coil quarternary structure. The α-helices of both synaptobrevin and syntaxin-1 bind to those of SNAP-25. Synaptobrevin binds the α-helix near SNAP-25's C-terminal side, while syntaxin-1 binds the α-helix near the N-terminus.[1]
SNAP-25 inhibits presynaptic P-, Q-, and L-type voltage-gated calcium channels[5] and interacts with the synaptotagmin C2B domain in Ca2+-independent fashion.[6] In glutamatergic synapses, SNAP-25 decreases the Ca2+ responsiveness, while it is naturally absent in GABAergic synapses.[7]
Two isoforms (mRNA splice variants) of SNAP-25 exist, which are labeled A and B. There are nine amino acid residue differences between the two isoforms, including a re-localization of one of the four cysteine residues.[8] 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[9] |
| Localization | Diffuse | Localized to terminals and varicosities[9] |
- ^ a b 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) - ^ 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) - ^ 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) - ^ Georgiev, Danko D .; James F . Glazebrook (2007). "Subneuronal processing of information by solitary waves and stochastic processes". In Lyshevski, Sergey Edward (ed.). Nano and Molecular Electronics Handbook. Nano and Microengineering Series. CRC Press. pp. 17-1–17-41. ISBN 978-0-8493-8528-5.
- ^ 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) - ^ a b 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.