SNAP25
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PDB 1jth | |
Proteína asociada ao sinaptosoma 25 (Synaptosomal-associated protein, 25kDa)
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Identificadores | |
Símbolo | SNAP25 |
Símbolos alt. | SNAP-25; CMS18; RIC-4; RIC4; SEC9; SNAP; bA416N4.2; dJ1068F16.2 |
Entrez | 6616 |
OMIM | |
RefSeq | NP_003072 |
UniProt | P60880 |
Outros datos | |
Locus | Cr. 20 :(10.22 – 10.31 Mb) |
A proteína asociada ao sinaptosoma 25 (SNAP25 ou SNAP-25 do inglés sinaptosomal-associated protein 25) é unha proteína t-SNARE de 25 kDa que está codificada en humanos no xene SNAP25 situado no cromosoma 20, que intervén na fusión das membranas das vesículas sinápticas durante a neurotransmisión.[1] A SNAP-25 é un compoñente do complexo trans-SNARE, o cal se propón para explicar a especificidade da fusión de membranas e para executar directamente a fusión ao formar un complexo apertado que une a membrana da vesícula sináptica cargada de neurotransmisor e a membrana plasmática da neurona presináptica.[2]
Estrutura e función
[editar | editar a fonte]![](http://178.128.105.246/content-http-upload.wikimedia.org/wikipedia/commons/thumb/9/90/Exocytosis-machinery.jpg/360px-Exocytosis-machinery.jpg)
A SNAP-25 é unha proteína Q-SNARE, ancorada na cara citosólica da membrana plasmática por medio de cadeas laterais palmitoíl unidas covalentemente a residuos do aminoácido cisteína do medio da molécula. Isto significa que SNAP-25 non contén un dominio transmembrana.[4]
A SNAP-25 foi identificada como a molécula que contribúe con dúas hélices α ao complexo SNARE, que é un dominio formado por un complexo de catro hélices α.[5] O complexo SNARE participa na fusión de vesículas, o cal implica o atraque e a fusión dunha vesícula coa membrana plasmática para realizar a exocitose. A sinaptobrevina, unha proteína que pertence á familia da proteína de membrana asociada a vesículas (VAMP), e a sintaxina-1 tamén contribúen a formar o conplexo SNARE proporcionando unha hélice α cada unha. A SNAP-25 ensámblase coa sinaptobrevina e a sintaxina-1 e a unión selectiva destas proteínas permite que se produza o atraque de vesículas e a fusión na súa correcta localización.[6]
Para formar o complexo SNARE, a sinaptobrevina, sintaxina-1, e SNAP-25 asócianse e empezan a enrolarse unha sobre as outras para formar unha estrutura cuaternaria de hélice superenrolada (coiled coil). As hélices α da sinaptobrevina e da sintaxina-1 únense ás da SNAP-25. A sinaptobrevina únese á hélice α preto do C-terminal de SNAP-25, mentres que a sintaxina-1 se une á hélice α preto do N-terminal.[4]
A SNAP-25 inhibe as canles de calcio reguladas por voltaxe dos tipos P, Q, e L presinápticos[7] e interacciona co dominio C2B da sinaptotagmina de modo independente do Ca2+.[8] En sinapses glutamatérxicas, a SNAP-25 fai diminuír a resposta ao Ca2+, mentres que está ausente de forma natural en sinapses GABAérxicas.[9]
Hai dúas isoformas (variantes de splicing alternativo do ARNm) da SNAP-25, que se denominan A e B. Hai nove diferenzas en residuos de aminoácidos entre estas dúas isoformas, incluíndo unha relocalización dun dos catro residuos de cisteína.[10] As principais características destas isoformas son as que se indican na táboa:
SNAP25A | SNAP25B | |
---|---|---|
Estrutura | -Hélice α N-terminal -Rexión de enlace (linker) de enrolamento aleatorio con catro cisteínas agrupadas cara ao centro |
-Hélice α N-teminal -Rexión de enlace de enrolamento aleatorio con catro cisteínas agrupadas cara ao extremo C-terminal |
Expresión | Principal isoforma de SNAP-25 en embrións e tecido neural en desenvolvemento.
Expresión mínima en tecidos adultos agás nos tecidos das glándulas pituitaria e adrenal |
Expresión mínima durante o desenvolvemento, principal isoforma en tecidos neurais adultos[11] |
Localización | Difusa | Localizada nos terminais e varicosidades[11] |
Importancia clínica
[editar | editar a fonte]En correspondencia coa súa resposta á regulación do Ca2+ sináptico, a deleción en heterocigotos do xene da SNAP-25 en ratos ten como resultado un fenotipo hiperactivo similar ao do trastorno por déficit de atención con hiperactividade (TDAH). En ratos heterocigotos, obsérvase unha diminución na hiperactividade tratándoos con dextroanfetamina (ou Dexedrina), un ingrediente activo do fármaco para TDAH Adderall. As delecións homocigotas do xene de SNAP-25 son letais. Estudos posteriores suxeriron que polo menos algunhas das mutacións no xene de SNAP-25 en humanos poderían predispoñer ao TDAH.[12][13]
Un estudo de asociación de xenoma amplo sinalou que o polimorfismo rs362584 neste xene estaba posiblemente asociado co trazo de personalidade de neuroticismo.[14] A toxinas botúlicas A, C e E clivan o SNAP-25[15] o que orixina a parálise no botulismo clinicamente desenvolvido.
Interaccións
[editar | editar a fonte]A SNAP-25 presenta interaccións con:
Notas
[editar | editar a fonte]- ↑ Maglott DR, Feldblyum TV, Durkin AS, Nierman WC (May 1996). "Radiation hybrid mapping of SNAP, PCSK2, and THBD (human chromosome 20p)". Mamm. Genome 7 (5): 400–1. PMID 8661740. doi:10.1007/s003359900120.
- ↑ Rizo J, Südhof TC (2002). "Snares and Munc18 in synaptic vesicle fusion". Nat Rev Neurosci 3 (8): 641–653. PMID 12154365. doi:10.1038/nrn898.
- ↑ Georgiev, Danko D; James F . Glazebrook (2007). "Subneuronal processing of information by solitary waves and stochastic processes". En Lyshevski, Sergey Edward. Nano and Molecular Electronics Handbook. Nano and Microengineering Series. CRC Press. pp. 17–1–17–41. ISBN 978-0-8493-8528-5. Arquivado dende o orixinal o 16 de xaneiro de 2016. Consultado o 13 de agosto de 2015.
- ↑ 4,0 4,1 Chapman ER, 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". J. Biol. Chem. 269 (44): 27427–32. PMID 7961655.
- ↑ Pevsner J, Hsu SC, Braun JE, Calakos N, Ting AE, Bennett MK, Scheller RH (1994). "Specificity and regulation of a synaptic vesicle docking complex". Neuron 13 (2): 353–61. PMID 8060616. doi:10.1016/0896-6273(94)90352-2.
- ↑ Calakos N, Bennett MK, Peterson KE, Scheller RH (1994). "Protein-protein interactions contributing to the specificity of intracellular vesicular trafficking". Science 263 (5150): 1146–9. PMID 8108733. doi:10.1126/science.8108733.
- ↑ Hodel A (October 1998). "SNAP-25". Int. J. Biochem. Cell Biol. 30 (10): 1069–73. PMID 9785471. doi:10.1016/S1357-2725(98)00079-X.
- ↑ Chapman ER (July 2002). "Synaptotagmin: a Ca(2+) sensor that triggers exocytosis?" (PDF). Nat. Rev. Mol. Cell Biol. 3 (7): 498–508. PMID 12094216. doi:10.1038/nrm855. Arquivado dende o orixinal (PDF) o 29 de agosto de 2006. Consultado o 13 de agosto de 2015.
- ↑ 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. PMID 14980208. doi:10.1016/S0896-6273(04)00077-7.
- ↑ Nagy G, Milosevic I, Fasshauer D, Müller EM, de Groot BL, Lang T, Wilson MC, Sørensen JB (December 2005). "Alternative splicing of SNAP-25 regulates secretion through nonconservative substitutions in the SNARE domain". Mol. Biol. Cell 16 (12): 5675–85. PMC 1289412. PMID 16195346. doi:10.1091/mbc.E05-07-0595.
- ↑ 11,0 11,1 Bark, Christina (February 1995). "Differential expression of SNAP-25 protein isoforms during divergent vesicle fusion events of neural development" (PDF). Proceedings of the Nation Academies of Sciences 92 (5): 1510–1514. doi:10.1073/pnas.92.5.1510. Consultado o 18 October 2014.
- ↑ Brophy K, Hawi Z, Kirley A, Fitzgerald M, Gill M (2002). "Synaptosomal-associated protein 25 (SNAP-25) and attention deficit hyperactivity disorder (ADHD): evidence of linkage and association in the Irish population". Mol. Psychiatry 7 (8): 913–7. PMID 12232787. doi:10.1038/sj.mp.4001092.
- ↑ Mill J, Curran S, Kent L, Gould A, Huckett L, Richards S, Taylor E, Asherson P (April 2002). "Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder". Am. J. Med. Genet. 114 (3): 269–71. PMID 11920846. doi:10.1002/ajmg.10253.
- ↑ Terracciano A, Sanna S, Uda M, Deiana B, Usala G, Busonero F, Maschio A, Scally M, Patriciu N, Chen WM, Distel MA, Slagboom EP, Boomsma DI, Villafuerte S, Sliwerska E, Burmeister M, Amin N, Janssens AC, van Duijn CM, Schlessinger D, Abecasis GR, Costa PT (October 2008). "Genome-wide association scan for five major dimensions of personality". Mol. Psychiatry 15 (6): 647–56. PMC 2874623. PMID 18957941. doi:10.1038/mp.2008.113.
- ↑ Aoki KR, Guyer B (November 2001). "Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions". Eur. J. Neurol. 8 Suppl 5: 21–9. PMID 11851731. doi:10.1046/j.1468-1331.2001.00035.x.
- ↑ 16,0 16,1 16,2 Chen X, Tomchick DR, Kovrigin E, Araç D, Machius M, Südhof TC, Rizo J (January 2002). "Three-dimensional structure of the complexin/SNARE complex". Neuron 33 (3): 397–409. PMID 11832227. doi:10.1016/s0896-6273(02)00583-4.
- ↑ Hu K, Carroll J, Rickman C, Davletov B (November 2002). "Action of complexin on SNARE complex". J. Biol. Chem. 277 (44): 41652–6. PMID 12200427. doi:10.1074/jbc.M205044200.
- ↑ Okamoto M, Schoch S, Südhof TC (June 1999). "EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25. A protein connection between exocytosis and endocytosis?". J. Biol. Chem. 274 (26): 18446–54. PMID 10373452. doi:10.1074/jbc.274.26.18446.
- ↑ Diefenbach RJ, Diefenbach E, Douglas MW, Cunningham AL (Dec 2002). "The heavy chain of conventional kinesin interacts with the SNARE proteins SNAP25 and SNAP23". Biochemistry 41 (50): 14906–15. PMID 12475239. doi:10.1021/bi026417u.
- ↑ 20,0 20,1 Ilardi JM, Mochida S, Sheng ZH (February 1999). "Snapin: a SNARE-associated protein implicated in synaptic transmission". Nat. Neurosci. 2 (2): 119–24. PMID 10195194. doi:10.1038/5673.
- ↑ 21,0 21,1 Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. PMID 16169070. doi:10.1016/j.cell.2005.08.029.
- ↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. PMID 16189514. doi:10.1038/nature04209.
- ↑ 23,0 23,1 23,2 23,3 Hata Y, Südhof TC (June 1995). "A novel ubiquitous form of Munc-18 interacts with multiple syntaxins. Use of the yeast two-hybrid system to study interactions between proteins involved in membrane traffic". J. Biol. Chem. 270 (22): 13022–8. PMID 7768895. doi:10.1074/jbc.270.22.13022.
- ↑ 24,0 24,1 24,2 24,3 Ravichandran V, Chawla A, Roche PA (June 1996). "Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues". J. Biol. Chem. 271 (23): 13300–3. PMID 8663154. doi:10.1074/jbc.271.23.13300.
- ↑ 25,0 25,1 25,2 Steegmaier M, Yang B, Yoo JS, Huang B, Shen M, Yu S, Luo Y, Scheller RH (Dec 1998). "Three novel proteins of the syntaxin/SNAP-25 family". J. Biol. Chem. 273 (51): 34171–9. PMID 9852078. doi:10.1074/jbc.273.51.34171.
- ↑ Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J (August 1999). "A conformational switch in syntaxin during exocytosis: role of munc18". EMBO J. 18 (16): 4372–82. PMC 1171512. PMID 10449403. doi:10.1093/emboj/18.16.4372.
- ↑ McMahon HT, Missler M, Li C, Südhof TC (October 1995). "Complexins: cytosolic proteins that regulate SNAP receptor function". Cell 83 (1): 111–9. PMID 7553862. doi:10.1016/0092-8674(95)90239-2.
- ↑ Gonelle-Gispert C, Molinete M, Halban PA, Sadoul K (September 2000). "Membrane localization and biological activity of SNAP-25 cysteine mutants in insulin-secreting cells". J. Cell. Sci. 113 ( Pt 18): 3197–205. PMID 10954418.
- ↑ 29,0 29,1 29,2 Li Y, Chin LS, Weigel C, Li L (November 2001). "Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis". J. Biol. Chem. 276 (44): 40824–33. PMID 11524423. doi:10.1074/jbc.M106141200.
- ↑ Chapman ER, An S, Barton N, Jahn R (November 1994). "SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils". J. Biol. Chem. 269 (44): 27427–32. PMID 7961655.
- ↑ Reed GL, Houng AK, Fitzgerald ML (April 1999). "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. PMID 10194441.
- ↑ Gerona RR, Larsen EC, Kowalchyk JA, Martin TF (March 2000). "The C terminus of SNAP25 is essential for Ca(2+)-dependent binding of synaptotagmin to SNARE complexes". J. Biol. Chem. 275 (9): 6328–36. PMID 10692432. doi:10.1074/jbc.275.9.6328.
- ↑ Zhang X, Kim-Miller MJ, Fukuda M, Kowalchyk JA, Martin TF (May 2002). "Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis". Neuron 34 (4): 599–611. PMID 12062043. doi:10.1016/s0896-6273(02)00671-2.
- ↑ Hao JC, Salem N, Peng XR, Kelly RB, Bennett MK (March 1997). "Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes". J. Neurosci. 17 (5): 1596–603. PMID 9030619.
Véxase tamén
[editar | editar a fonte]Bibliografía
[editar | editar a fonte]- Hanson PI, Otto H, Barton N, Jahn R (1995). "The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin.". J. Biol. Chem. 270 (28): 16955–61. PMID 7622514. doi:10.1074/jbc.270.28.16955.
- Hata Y, Südhof TC (1995). "A novel ubiquitous form of Munc-18 interacts with multiple syntaxins. Use of the yeast two-hybrid system to study interactions between proteins involved in membrane traffic.". J. Biol. Chem. 270 (22): 13022–8. PMID 7768895. doi:10.1074/jbc.270.22.13022.
- Chapman ER, 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.". J. Biol. Chem. 269 (44): 27427–32. PMID 7961655.
- Zhao N, Hashida H, Takahashi N, Sakaki Y (1994). "Cloning and sequence analysis of the human SNAP25 cDNA.". Gene 145 (2): 313–4. PMID 8056350. doi:10.1016/0378-1119(94)90027-2.
- Bark IC, Wilson MC (1994). "Human cDNA clones encoding two different isoforms of the nerve terminal protein SNAP-25.". Gene 139 (2): 291–2. PMID 8112622. doi:10.1016/0378-1119(94)90773-0.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. PMID 8125298. doi:10.1016/0378-1119(94)90802-8.
- Maglott DR, Feldblyum TV, Durkin AS, Nierman WC (1996). "Radiation hybrid mapping of SNAP, PCSK2, and THBD (human chromosome 20p).". Mamm. Genome 7 (5): 400–1. PMID 8661740. doi:10.1007/s003359900120.
- Ravichandran V, Chawla A, Roche PA (1996). "Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues.". J. Biol. Chem. 271 (23): 13300–3. PMID 8663154. doi:10.1074/jbc.271.23.13300.
- Rettig J, Sheng ZH, Kim DK, Hodson CD, Snutch TP, Catterall WA (1996). "Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25.". Proc. Natl. Acad. Sci. U.S.A. 93 (14): 7363–8. PMC 38990. PMID 8692999. doi:10.1073/pnas.93.14.7363.
- Jagadish MN, Fernandez CS, Hewish DR, Macaulay SL, Gough KH, Grusovin J, Verkuylen A, Cosgrove L, Alafaci A, Frenkel MJ, Ward CW (1996). "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.". Biochem. J. 317 (3): 945–54. PMC 1217577. PMID 8760387.
- Betz A, Okamoto M, Benseler F, Brose N (1997). "Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin.". J. Biol. Chem. 272 (4): 2520–6. PMID 8999968. doi:10.1074/jbc.272.4.2520.
- Araki S, Tamori Y, Kawanishi M, Shinoda H, Masugi J, Mori H, Niki T, Okazawa H, Kubota T, Kasuga M (1997). "Inhibition of the binding of SNAP-23 to syntaxin 4 by Munc18c.". Biochem. Biophys. Res. Commun. 234 (1): 257–62. PMID 9168999. doi:10.1006/bbrc.1997.6560.
- Lane SR, Liu Y (1997). "Characterization of the palmitoylation domain of SNAP-25.". J. Neurochem. 69 (5): 1864–9. PMID 9349529. doi:10.1046/j.1471-4159.1997.69051864.x.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. PMID 9373149. doi:10.1016/S0378-1119(97)00411-3.
- Okamoto M, Südhof TC (1998). "Mints, Munc18-interacting proteins in synaptic vesicle exocytosis.". J. Biol. Chem. 272 (50): 31459–64. PMID 9395480. doi:10.1074/jbc.272.50.31459.
- Low SH, Roche PA, Anderson HA, van Ijzendoorn SC, Zhang M, Mostov KE, Weimbs T (1998). "Targeting of SNAP-23 and SNAP-25 in polarized epithelial cells.". J. Biol. Chem. 273 (6): 3422–30. PMID 9452464. doi:10.1074/jbc.273.6.3422.
- Poirier MA, Hao JC, Malkus PN, Chan C, Moore MF, King DS, Bennett MK (1998). "Protease resistance of syntaxin.SNAP-25.VAMP complexes. Implications for assembly and structure.". J. Biol. Chem. 273 (18): 11370–7. PMID 9556632. doi:10.1074/jbc.273.18.11370.
- Prekeris R, Klumperman J, Chen YA, Scheller RH (1998). "Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes.". J. Cell Biol. 143 (4): 957–71. PMC 2132958. PMID 9817754. doi:10.1083/jcb.143.4.957.
- Gonelle-Gispert C, Halban PA, Niemann H, Palmer M, Catsicas S, Sadoul K (1999). "SNAP-25a and -25b isoforms are both expressed in insulin-secreting cells and can function in insulin secretion.". Biochem. J. 339 (1): 159–65. PMC 1220140. PMID 10085240. doi:10.1042/0264-6021:3390159.
- Ilardi JM, Mochida S, Sheng ZH (1999). "Snapin: a SNARE-associated protein implicated in synaptic transmission.". Nat. Neurosci. 2 (2): 119–24. PMID 10195194. doi:10.1038/5673.
Ligazóns externas
[editar | editar a fonte]- SNAP25 Protein Medical Subject Headings (MeSH) na Biblioteca Nacional de Medicina dos EUA.
Este artigo contén textos procedentes de Pfam e InterPro IPR000928 en dominio público.