Sintaxina 1A

A Sintaxina 1A (STX1A ou STX1) é unha proteína codificada nos humanos no xene STX1A do cromosoma 7, que intervén na fusión de membranas durante a exocitose.^[1]

PDB 1bro
Identificadores
Símbolo	STX1A
Símbolos alt.	HPC-1; P35-1; STX1; SYN1A
Entrez	6804
OMIM	186590
RefSeq	NP_001159375
UniProt	Q16623
Outros datos
Locus	Cr. 7 :(73.7 – 73.72 Mb)

Función

As vesículas sinápticas almacenan neurotransmisores que son liberados durante a exocitose regulada polo calcio. A especificidade da liberación do neurotransmisor require a localización das vesículas sinápticas e dos canles de calcio na zona activa presináptica. As sintaxinas actúan neste proceso de fusión de vesículas.

A sintaxina 1A é un membro da superfamilia da sintaxina. As sintaxinas son proteínas específicas do sistema nervioso implicadas no atraque de vesículas sinápticas na membrana plasmática presináptica. As sintaxinas posúen un só dominio C-terminal transmembrana, un dominio SNARE (chamado H3), e un dominio regulador N-terminal (Habc). As sintaxinas únense á sinaptotagmina dun modo dependente do calcio e interaccionan con canles de calcio e potasio reguladas por voltaxe por medio do seu dominio C-terminal H3. A sintaxina 1A é unha proteína clave na regulación do canle iónica e na exocitose sináptica.^[2]

Importancia clínica

As sintaxinas serven como substrato para a neurotoxina botúlica tipo C, unha metaloprotease que bloquea a exocitose e ten unha alta afinidade por un complexo molecular no que está incluído o receptor de alfa-latrotoxina, que produce unha exocitose explosiva.^[3]

O nivel de expresión de STX1A está correlacionado directamente coa intelixencia na síndrome de Williams.^[4]

Interaccións

STX1A presenta interaccións con:

• CPLX1,^[5][6][7]
• CFTR,^[8][9]
• NAPA,^[10][11]
• RNF40,^[12]
• SCNN1G,^[13]
• SLC6A1,^[14][15][16]
• SNAP-25,^{[5][6][10][17][18][19][20][21][22][23][24]}
• SNAP23,^{[22][24][25][26][27]}
• STXBP1,^{[5][10][18][28][29]}
• STXBP5,^[30][31]
• SYT1^[32][33]
• UNC13B,^[34]
• VAMP2,^{[5][6][10][29][35][36]} e
• VAMP8.^[37]

Notas

1. Bennett MK, Calakos N, Scheller RH (Aug 1992). "Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones". Science 257 (5067): 255–9. PMID 1321498. doi:10.1126/science.1321498.
2. "Entrez Gene: STX1A syntaxin 1A (brain)".
3. Zhang R, Maksymowych AB, Simpson LL (July 1995). "Cloning and sequence analysis of a cDNA encoding human syntaxin 1A, a polypeptide essential for exocytosis". Gene 159 (2): 293–4. PMID 7622072. doi:10.1016/0378-1119(95)00152-V.
4. Gao MC, Bellugi U, Dai L, Mills DL, Sobel EM, Lange K, Korenberg JR (2010). Toland, Amanda Ewart, ed. "Intelligence in Williams Syndrome Is Related to STX1A, Which Encodes a Component of the Presynaptic SNARE Complex". PLoS ONE 5 (4): e10292. PMC 2858212. PMID 20422020. doi:10.1371/journal.pone.0010292. Resumo divulgativo – The Salt Lake Tribune.
5. 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.
6. 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.
7. 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.
8. Naren AP, Nelson DJ, Xie W, Jovov B, Pevsner J, Bennett MK, Benos DJ, Quick MW, Kirk KL (November 1997). "Regulation of CFTR chloride channels by syntaxin and Munc18 isoforms". Nature 390 (6657): 302–5. PMID 9384384. doi:10.1038/36882.
9. Cormet-Boyaka E, Di A, Chang SY, Naren AP, Tousson A, Nelson DJ, Kirk KL (September 2002). "CFTR chloride channels are regulated by a SNAP-23/syntaxin 1A complex". Proc. Natl. Acad. Sci. U.S.A. 99 (19): 12477–82. PMC 129470. PMID 12209004. doi:10.1073/pnas.192203899.
10. 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.
11. Hanson PI, Otto H, Barton N, Jahn R (July 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.
12. Chin LS, Vavalle JP, Li L (September 2002). "Staring, a novel E3 ubiquitin-protein ligase that targets syntaxin 1 for degradation". J. Biol. Chem. 277 (38): 35071–9. PMID 12121982. doi:10.1074/jbc.M203300200.
13. Berdiev BK, Jovov B, Tucker WC, Naren AP, Fuller CM, Chapman ER, Benos DJ (June 2004). "ENaC subunit-subunit interactions and inhibition by syntaxin 1A". Am. J. Physiol. Renal Physiol. 286 (6): F1100–6. PMID 14996668. doi:10.1152/ajprenal.00344.2003.
14. Beckman ML, Bernstein EM, Quick MW (August 1998). "Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A". J. Neurosci. 18 (16): 6103–12. PMID 9698305.
15. Quick MW (April 2002). "Substrates regulate γ-aminobutyric acid transporters in a syntaxin 1A-dependent manner". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5686–91. PMC 122832. PMID 11960023. doi:10.1073/pnas.082712899.
16. Deken SL, Beckman ML, Boos L, Quick MW (October 2000). "Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A". Nat. Neurosci. 3 (10): 998–1003. PMID 11017172. doi:10.1038/79939.
17. 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.
18. 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.
19. 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 (18): 3197–205. PMID 10954418.
20. 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. 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.
22. 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.
23. 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.
24. Steegmaier M, Yang B, Yoo JS, Huang B, Shen M, Yu S, Luo Y, Scheller RH (December 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.
25. Imai A, Nashida T, Yoshie S, Shimomura H (August 2003). "Intracellular localisation of SNARE proteins in rat parotid acinar cells: SNARE complexes on the apical plasma membrane". Arch. Oral Biol. 48 (8): 597–604. PMID 12828989. doi:10.1016/S0003-9969(03)00116-X.
26. Li G, Alexander EA, Schwartz JH (May 2003). "Syntaxin isoform specificity in the regulation of renal H+-ATPase exocytosis". J. Biol. Chem. 278 (22): 19791–7. PMID 12651853. doi:10.1074/jbc.M212250200.
27. Araki S, Tamori Y, Kawanishi M, Shinoda H, Masugi J, Mori H, Niki T, Okazawa H, Kubota T, Kasuga M (May 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.
28. Bhaskar K, Shareef MM, Sharma VM, Shetty AP, Ramamohan Y, Pant HC, Raju TR, Shetty KT (January 2004). "Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins". Neurochem. Int. 44 (1): 35–44. PMID 12963086. doi:10.1016/S0197-0186(03)00099-8.
29. Pérez-Brangulí F, Muhaisen A, Blasi J (June 2002). "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". Mol. Cell. Neurosci. 20 (2): 169–80. PMID 12093152. doi:10.1006/mcne.2002.1122.
30. Widberg CH, Bryant NJ, Girotti M, Rea S, James DE (September 2003). "Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation". J. Biol. Chem. 278 (37): 35093–101. PMID 12832401. doi:10.1074/jbc.M304261200.
31. Fujita Y, Shirataki H, Sakisaka T, Asakura T, Ohya T, Kotani H, Yokoyama S, Nishioka H, Matsuura Y, Mizoguchi A, Scheller RH, Takai Y (May 1998). "Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process". Neuron 20 (5): 905–15. PMID 9620695. doi:10.1016/S0896-6273(00)80472-9.
32. Shao X, Li C, Fernandez I, Zhang X, Südhof TC, Rizo J (January 1997). "Synaptotagmin-syntaxin interaction: the C2 domain as a Ca2+-dependent electrostatic switch". Neuron 18 (1): 133–42. PMID 9010211. doi:10.1016/S0896-6273(01)80052-0.
33. Thomas DM, Ferguson GD, Herschman HR, Elferink LA (July 1999). "Functional and Biochemical Analysis of the C2 Domains of Synaptotagmin IV". Mol. Biol. Cell 10 (7): 2285–95. PMC 25443. PMID 10397765. doi:10.1091/mbc.10.7.2285.
34. Betz A, Okamoto M, Benseler F, Brose N (January 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.
35. Margittai M, Otto H, Jahn R (March 1999). "A stable interaction between syntaxin 1a and synaptobrevin 2 mediated by their transmembrane domains". FEBS Lett. 446 (1): 40–4. PMID 10100611. doi:10.1016/S0014-5793(99)00028-9.
36. 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.
37. Nagamatsu S, Nakamichi Y, Watanabe T, Matsushima S, Yamaguchi S, Ni J, Itagaki E, Ishida H (January 2001). "Localization of cellubrevin-related peptide, endobrevin, in the early endosome in pancreatic beta cells and its physiological function in exo-endocytosis of secretory granules". J. Cell. Sci. 114 (Pt 1): 219–227. PMID 11112705.

Véxase tamén

Bibliografía

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• Zhang R, Maksymowych AB, Simpson LL (1995). "Cloning and sequence analysis of a cDNA encoding human syntaxin 1A, a polypeptide essential for exocytosis". Gene 159 (2): 293–4. PMID 7622072. doi:10.1016/0378-1119(95)00152-V.
• 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.
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