syntaxin 1


Summary: A neuronal cell membrane protein that combines with SNAP-25 and SYNAPTOBREVIN 2 to form a SNARE complex that leads to EXOCYTOSIS.

Top Publications

  1. Deak F, Shin O, Kavalali E, Sudhof T. Structural determinants of synaptobrevin 2 function in synaptic vesicle fusion. J Neurosci. 2006;26:6668-76 pubmed
    ..Furthermore, the fusion reactions underlying evoked and spontaneous release differ mechanistically. ..
  2. James D, Kowalchyk J, Daily N, Petrie M, Martin T. CAPS drives trans-SNARE complex formation and membrane fusion through syntaxin interactions. Proc Natl Acad Sci U S A. 2009;106:17308-13 pubmed publisher
    ..The results revealed an unexpected activity of a priming protein to accelerate fusion by efficiently promoting trans-SNARE complex formation. CAPS may function in priming by organizing SNARE complexes on the plasma membrane. ..
  3. Chen X, Lu J, Dulubova I, Rizo J. NMR analysis of the closed conformation of syntaxin-1. J Biomol NMR. 2008;41:43-54 pubmed publisher
  4. Wang D, Deken S, Whitworth T, Quick M. Syntaxin 1A inhibits GABA flux, efflux, and exchange mediated by the rat brain GABA transporter GAT1. Mol Pharmacol. 2003;64:905-13 pubmed
  5. Gerber S, Rah J, Min S, Liu X, de Wit H, Dulubova I, et al. Conformational switch of syntaxin-1 controls synaptic vesicle fusion. Science. 2008;321:1507-10 pubmed publisher
    ..Thus, the closed conformation of syntaxin-1 gates the initiation of the synaptic vesicle fusion reaction, which is then mediated by SNARE-complex/Munc18-1 assemblies. ..
  6. Bonanno G, Giambelli R, Raiteri L, Tiraboschi E, Zappettini S, Musazzi L, et al. Chronic antidepressants reduce depolarization-evoked glutamate release and protein interactions favoring formation of SNARE complex in hippocampus. J Neurosci. 2005;25:3270-9 pubmed
    ..membranes of chronically treated rats we found a marked reduction in the protein-protein interaction between syntaxin 1 and Thr286-phosphorylated alphaCaM kinase II (alpha-calcium/calmodulin-dependent protein kinase II) (an ..
  7. Jarvis S, Barr W, Feng Z, Hamid J, Zamponi G. Molecular determinants of syntaxin 1 modulation of N-type calcium channels. J Biol Chem. 2002;277:44399-407 pubmed
    ..Neurosci. 21, 2939-2948). Here, we have investigated the molecular determinants that govern the action of syntaxin 1 isoforms on N-type calcium channel function...
  8. Proux Gillardeaux V, Galli T, Callebaut I, Mikhailik A, Calothy G, Marx M. D53 is a novel endosomal SNARE-binding protein that enhances interaction of syntaxin 1 with the synaptobrevin 2 complex in vitro. Biochem J. 2003;370:213-21 pubmed
    ..Furthermore, D53 forms Sb2/Stx1/D53 complexes in vitro in a manner similar to SNAP-25. We propose that D53 could be involved in the assembly or disassembly of endosomal SNARE complexes by regulating Sb2/Stx interaction. ..
  9. Melia T, You D, Tareste D, Rothman J. Lipidic antagonists to SNARE-mediated fusion. J Biol Chem. 2006;281:29597-605 pubmed
    ..In this regard, physiologically docked exocytic vesicles may be anchored by a highly dynamic and potentially even reversible SNAREpin. ..

More Information


  1. Smith R, Klein P, Koc Schmitz Y, Waldvogel H, Faull R, Brundin P, et al. Loss of SNAP-25 and rabphilin 3a in sensory-motor cortex in Huntington's disease. J Neurochem. 2007;103:115-23 pubmed
    ..Thus, levels of synaptobrevin II, syntaxin 1, rab3a or synaptophysin are unaltered in the same patient samples...
  2. James D, Khodthong C, Kowalchyk J, Martin T. Phosphatidylinositol 4,5-bisphosphate regulates SNARE-dependent membrane fusion. J Cell Biol. 2008;182:355-66 pubmed publisher
    ..These results indicate that PI 4,5-P(2) regulates fusion both as a fusion restraint that syntaxin-1 alleviates and as an essential cofactor that recruits protein priming factors to facilitate SNARE-dependent fusion. ..
  3. Peng L, Liu H, Ruan H, Tepp W, Stoothoff W, Brown R, et al. Cytotoxicity of botulinum neurotoxins reveals a direct role of syntaxin 1 and SNAP-25 in neuron survival. Nat Commun. 2013;4:1472 pubmed publisher
    ..Whether BoNTs disrupt additional neuronal functions has not been addressed. Here we report that cleavage of syntaxin 1 by BoNT/C, and cleavage of SNAP-25 by BoNT/E both induce degeneration of neurons...
  4. Khvotchev M, Dulubova I, Sun J, Dai H, Rizo J, Sudhof T. Dual modes of Munc18-1/SNARE interactions are coupled by functionally critical binding to syntaxin-1 N terminus. J Neurosci. 2007;27:12147-55 pubmed
    ..Viewed together, our data indicate that binding of Munc18 to the syntaxin N terminus unites different modes of Munc18/SNARE interactions and is essential for exocytic membrane fusion. ..
  5. Murray D, Tamm L. Clustering of syntaxin-1A in model membranes is modulated by phosphatidylinositol 4,5-bisphosphate and cholesterol. Biochemistry. 2009;48:4617-25 pubmed publisher
    ..Possible implications of these results to the regulation of SNARE-mediated membrane fusion are discussed. ..
  6. Hatsuzawa K, Lang T, Fasshauer D, Bruns D, Jahn R. The R-SNARE motif of tomosyn forms SNARE core complexes with syntaxin 1 and SNAP-25 and down-regulates exocytosis. J Biol Chem. 2003;278:31159-66 pubmed
    ..Here we show that tomosyn forms genuine SNARE core complexes with the SNAREs syntaxin 1 and SNAP-25...
  7. van Loon J, Leebeek F, Deckers J, Dippel D, Poldermans D, Strachan D, et al. Effect of genetic variations in syntaxin-binding protein-5 and syntaxin-2 on von Willebrand factor concentration and cardiovascular risk. Circ Cardiovasc Genet. 2010;3:507-12 pubmed publisher
    ..Furthermore, in our study, genetic variability in STX2 is associated with the risk of arterial thrombosis. However, at this point, the underlying mechanism remains unclear. ..
  8. Zhang Z, Takeuchi H, Gao J, Wang D, James D, Martin T, et al. PRIP (phospholipase C-related but catalytically inactive protein) inhibits exocytosis by direct interactions with syntaxin 1 and SNAP-25 through its C2 domain. J Biol Chem. 2013;288:7769-80 pubmed publisher
    ..In this study, we found that the C2 domain of PRIP directly interacts with syntaxin 1 and SNAP-25 but not with VAMP2...
  9. Palmer Z, Duncan R, Johnson J, Lian L, Mello L, Booth D, et al. S-nitrosylation of syntaxin 1 at Cys(145) is a regulatory switch controlling Munc18-1 binding. Biochem J. 2008;413:479-91 pubmed publisher
    ..Thus S-nitrosylation of Cys(145) may be a molecular switch to disrupt Munc18-1 binding to the closed conformation of syntaxin 1a, thereby facilitating its engagement with the membrane fusion machinery. ..
  10. Sakisaka T, Baba T, Tanaka S, Izumi G, Yasumi M, Takai Y. Regulation of SNAREs by tomosyn and ROCK: implication in extension and retraction of neurites. J Cell Biol. 2004;166:17-25 pubmed
    ..Thus, tomosyn demarcates the plasma membrane by binding to syntaxin-1 phosphorylated by ROCK, and thereby regulates extension and retraction of neurites. ..
  11. Tsuboi T, Fukuda M. The Slp4-a linker domain controls exocytosis through interaction with Munc18-1.syntaxin-1a complex. Mol Biol Cell. 2006;17:2101-12 pubmed
    ..Our findings reveal a novel docking machinery for dense-core vesicle exocytosis: Slp4-a simultaneously interacts with Rab27A and Munc18-1 on the dense-core vesicle and with syntaxin-1a in the plasma membrane. ..
  12. Toonen R, de Vries K, Zalm R, Sudhof T, Verhage M. Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation. J Neurochem. 2005;93:1393-400 pubmed
    ..Munc18-1 binds tightly to the SNARE protein syntaxin 1, but the physiological significance and functional role of this interaction remain unclear...
  13. Sieber J, Willig K, Heintzmann R, Hell S, Lang T. The SNARE motif is essential for the formation of syntaxin clusters in the plasma membrane. Biophys J. 2006;90:2843-51 pubmed
    In the plasma membrane, syntaxin 1 and syntaxin 4 clusters define sites at which secretory granules and caveolae fuse, respectively...
  14. Arunachalam L, Han L, Tassew N, He Y, Wang L, Xie L, et al. Munc18-1 is critical for plasma membrane localization of syntaxin1 but not of SNAP-25 in PC12 cells. Mol Biol Cell. 2008;19:722-34 pubmed
  15. Leung Y, Kwan E, Ng B, Kang Y, Gaisano H. SNAREing voltage-gated K+ and ATP-sensitive K+ channels: tuning beta-cell excitability with syntaxin-1A and other exocytotic proteins. Endocr Rev. 2007;28:653-63 pubmed
    ..This review discusses this interesting aspect that exocytotic proteins not only promote secretion per se, but also fine-tune beta-cell excitability via modulation of ion channel gating. ..
  16. Cohen Kutner M, Nachmanni D, Atlas D. CaV2.1 (P/Q channel) interaction with synaptic proteins is essential for depolarization-evoked release. Channels (Austin). 2010;4:266-77 pubmed
  17. Kauppi M, Wohlfahrt G, Olkkonen V. Analysis of the Munc18b-syntaxin binding interface. Use of a mutant Munc18b to dissect the functions of syntaxins 2 and 3. J Biol Chem. 2002;277:43973-9 pubmed
    ..This suggests that, although syntaxin 3 is the main target SNARE operating in exocytic transport to the apical plasma membrane in certain epithelial cell types, syntaxin 2 may play an important role in this trafficking route in others. ..
  18. Matos M, Mukherjee K, Chen X, Rizo J, Sudhof T. Evidence for SNARE zippering during Ca2+-triggered exocytosis in PC12 cells. Neuropharmacology. 2003;45:777-86 pubmed into a four-helical bundle with SNARE motifs from the plasma membrane SNARE proteins syntaxin 1 and SNAP-25...
  19. Melia T, Weber T, McNew J, Fisher L, Johnston R, Parlati F, et al. Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins. J Cell Biol. 2002;158:929-40 pubmed
    ..Proteins that stabilize or destabilize one or the other state of the tC fusion switch would exert fine temporal control over the rate of fusion after SNAREs have already partly zippered up. ..
  20. Cao Z, Wang Y, McAdory B, Kemp M, Ivy M, Newkirk R, et al. Identification and characterization of syntaxin 1 antisense variants in Limulus polyphemus. Cell Mol Neurobiol. 2006;26:53-66 pubmed
    1.A Limulus SMART(TM) cDNA library screening resulted in the cloning of four syntaxin 1 homologs (referred to as Limulus syntaxin [Lim-syn] 1A, 1B, 1C, and 1D) (Wang, Y., Cao, Z., Xu, W., Kemp, M. D., McAdory, B. S., Newkirk, R. F...
  21. Hu S, Christie M, Saez N, Latham C, Jarrott R, Lua L, et al. Possible roles for Munc18-1 domain 3a and Syntaxin1 N-peptide and C-terminal anchor in SNARE complex formation. Proc Natl Acad Sci U S A. 2011;108:1040-5 pubmed publisher
    ..We hypothesize that Munc18-1 domain 3a undergoes a conformational change that may allow coiled-coil interactions with SNARE complexes. ..
  22. Maeda Y, Kashiwazaki J, Shimoda C, Nakamura T. The Schizosaccharomyces pombe syntaxin 1 homolog, Psy1, is essential in the development of the forespore membrane. Biosci Biotechnol Biochem. 2009;73:339-45 pubmed
    ..In the fission yeast Schizosaccharomyces pombe, the psy1(+) gene encoding a syntaxin 1 homolog was originally isolated as a multicopy suppressor of the sporulation-deficient mutant, spo3, but little ..
  23. Yang R, Ma H, Thomas S, Kinnamon J. Immunocytochemical analysis of syntaxin-1 in rat circumvallate taste buds. J Comp Neurol. 2007;502:883-93 pubmed
    ..These results support the proposition that taste cell synapses use classical SNARE machinery such as syntaxin-1 for neurotransmitter release in rat circumvallate taste buds. ..
  24. Sieber J, Willig K, Kutzner C, Gerding Reimers C, Harke B, Donnert G, et al. Anatomy and dynamics of a supramolecular membrane protein cluster. Science. 2007;317:1072-6 pubmed
    ..With syntaxin 1 as an example, we applied a combination of far-field optical nanoscopy, biochemistry, fluorescence recovery ..
  25. Ohara Imaizumi M, Nishiwaki C, Kikuta T, Kumakura K, Nakamichi Y, Nagamatsu S. Site of docking and fusion of insulin secretory granules in live MIN6 beta cells analyzed by TAT-conjugated anti-syntaxin 1 antibody and total internal reflection fluorescence microscopy. J Biol Chem. 2004;279:8403-8 pubmed
    ..we analyzed the interaction between the docking/fusion of green fluorescent protein-tagged insulin granules and syntaxin 1 labeled by TAT-conjugated Cy3-labeled antibody (Ab) using total internal reflection fluorescence microscopy (..
  26. Degtyar V, Hafez I, Bray C, Zucker R. Dance of the SNAREs: assembly and rearrangements detected with FRET at neuronal synapses. J Neurosci. 2013;33:5507-23 pubmed publisher
  27. Okugawa Y, Hirai Y. Overexpression of extracellular epimorphin leads to impaired epidermal differentiation in HaCaT keratinocytes. J Invest Dermatol. 2008;128:1884-93 pubmed publisher
  28. Pobbati A, Razeto A, Böddener M, Becker S, Fasshauer D. Structural basis for the inhibitory role of tomosyn in exocytosis. J Biol Chem. 2004;279:47192-200 pubmed
    ..Moreover, data bank searches revealed that the R-SNARE motif of tomosyn is highly conserved throughout all eukaryotic kingdoms. This suggests that the formation of a tight SNARE complex is important for the function of tomosyn. ..
  29. Cohen R, Atlas D. R-type voltage-gated Ca(2+) channel interacts with synaptic proteins and recruits synaptotagmin to the plasma membrane of Xenopus oocytes. Neuroscience. 2004;128:831-41 pubmed
    ..We propose that the distinct kinetics of the Ca(2+)-channel acquired by the close association with the vesicle and the t-SNAREs within the excitosome complex may be essential for depolarization evoked transmitter release. ..
  30. Zhang W, Lilja L, Mandic S, Gromada J, Smidt K, Janson J, et al. Tomosyn is expressed in beta-cells and negatively regulates insulin exocytosis. Diabetes. 2006;55:574-81 pubmed
    ..b>Syntaxin 1 coimmunoprecipitated with tomosyn in extracts of insulin-secreting cells...
  31. Shen J, Tareste D, Paumet F, Rothman J, Melia T. Selective activation of cognate SNAREpins by Sec1/Munc18 proteins. Cell. 2007;128:183-95 pubmed
    ..Munc18-1 accelerates fusion only for the cognate SNAREs for exocytosis, therefore enhancing fusion specificity. ..
  32. Lang T, Margittai M, Hölzler H, Jahn R. SNAREs in native plasma membranes are active and readily form core complexes with endogenous and exogenous SNAREs. J Cell Biol. 2002;158:751-60 pubmed
    ..Our data show that virtually all of the endogenous syntaxin 1 and SNAP-25 are highly reactive and readily form SNARE complexes with exogenously added SNAREs...
  33. Mitchell S, Ryan T. Munc18-dependent regulation of synaptic vesicle exocytosis by syntaxin-1A in hippocampal neurons. Neuropharmacology. 2005;48:372-80 pubmed
    ..Our results also indicate that syntaxin can control the frequency-response characteristics of the presynaptic fusion machinery. ..
  34. Park W, Lee S, Kwon N, Baek K, Kim D, Yun H. Leucine-rich glioma inactivated 3 associates with syntaxin 1. Neurosci Lett. 2008;444:240-4 pubmed publisher
    ..In this study, we identified syntaxin 1, a SNARE component in exocytosis, as a candidate functional target of LGI3...
  35. Rathore S, Bend E, Yu H, Hammarlund M, Jorgensen E, Shen J. Syntaxin N-terminal peptide motif is an initiation factor for the assembly of the SNARE-Sec1/Munc18 membrane fusion complex. Proc Natl Acad Sci U S A. 2010;107:22399-406 pubmed publisher
    ..After association, Munc18-1 and the SNARE bundle together drive membrane merging without further involving the N-peptide. Thus, the syntaxin N-peptide is an initiation factor for the assembly of the SNARE-SM membrane fusion complex. ..
  36. Li C, Roy K, Dandridge K, Naren A. Molecular assembly of cystic fibrosis transmembrane conductance regulator in plasma membrane. J Biol Chem. 2004;279:24673-84 pubmed
    ..Our studies provide a deeper understanding of how the CFTR assembly takes place in native cell membrane. ..
  37. Pickett J, Thorn P, Edwardson J. The plasma membrane Q-SNARE syntaxin 2 enters the zymogen granule membrane during exocytosis in the pancreatic acinar cell. J Biol Chem. 2005;280:1506-11 pubmed
    ..We conclude that syntaxin 2 enters the membrane of a fused zymogen granule after the opening of the fusion pore, and we suggest that this movement might permit the onset of secondary fusion. ..
  38. Hu C, Ahmed M, Melia T, Sollner T, Mayer T, Rothman J. Fusion of cells by flipped SNAREs. Science. 2003;300:1745-9 pubmed
    ..Here, cells expressing the interacting domains of v- and t-SNAREs on the cell surface were found to fuse spontaneously, demonstrating that SNAREs are sufficient to fuse biological membranes. ..
  39. Miura K, Yoshino R, Hirai Y, Goto T, Ohshima S, Mikami K, et al. Epimorphin, a morphogenic protein, induces proteases in rodent hepatocytes through NF-kappaB. J Hepatol. 2007;47:834-43 pubmed
    ..In addition, NF-kappaB activation was also required for spheroid formation. Epimorphin elicits hepatocyte spheroids by inducing proteases in rodent hepatocytes through NF-kappaB. ..
  40. Takahashi N, Hatakeyama H, Okado H, Noguchi J, Ohno M, Kasai H. SNARE conformational changes that prepare vesicles for exocytosis. Cell Metab. 2010;12:19-29 pubmed publisher
    ..Thus, SNARE proteins exist in multiple stable preparatory configurations, from which Ca(2+) may trigger exocytosis through distinct mechanisms and with distinct kinetics...
  41. Shirasaka T, Iizuka M, Yukawa M, Hirai Y, Horie Y, Itou H, et al. Altered expression of epimorphin in ulcerative colitis. J Gastroenterol Hepatol. 2003;18:570-7 pubmed
    ..Our results suggest that altered expression of epimorphin contributes to impaired healing and chronic inflammation in the colonic mucosa of UC patients. ..
  42. Li G, Yang Q, Alexander E, Schwartz J. Syntaxin 1A has a specific binding site in the H3 domain that is critical for targeting of H+-ATPase to apical membrane of renal epithelial cells. Am J Physiol Cell Physiol. 2005;289:C665-72 pubmed
    ..We conclude that within the H3 domain of syntaxin 1A is a unique cassette that participates in the binding of the H(+)-ATPase to the apical membrane and confers specificity of syntaxin 1A in the process of H(+)-ATPase exocytosis. ..
  43. Zhou P, Pang Z, Yang X, Zhang Y, Rosenmund C, Bacaj T, et al. Syntaxin-1 N-peptide and Habc-domain perform distinct essential functions in synaptic vesicle fusion. EMBO J. 2013;32:159-71 pubmed publisher
    ..Thus, the N-terminal syntaxin-1 domains mediate different functions in synaptic vesicle fusion, probably via formation of distinct Munc18/SNARE-protein complexes. ..
  44. Quintanar J, Salinas E. Effect of hypothyroidism on synaptosomal-associated protein of 25 kDa and syntaxin-1 expression in adenohypophyses of rat. J Endocrinol Invest. 2002;25:754-8 pubmed
    ..In conclusion, thyroidectomy produces changes in both expression and immunoreactivity of SNAP-25 and syntaxin-1 in adenohypophyses of rats and these effects can be reversed by T4 administration. ..
  45. Berdiev B, Jovov B, Tucker W, Naren A, Fuller C, Chapman E, et al. ENaC subunit-subunit interactions and inhibition by syntaxin 1A. Am J Physiol Renal Physiol. 2004;286:F1100-6 pubmed
    ..Our findings provide evidence for a direct physical interaction between ENaC and syntaxin 1A and suggest involvement of ENaC's cytoplasmic domains in functional modulation of ENaC activity by syntaxin 1A. ..
  46. Leung Y, Kang Y, Xia F, Sheu L, Gao X, Xie H, et al. Open form of syntaxin-1A is a more potent inhibitor than wild-type syntaxin-1A of Kv2.1 channels. Biochem J. 2005;387:195-202 pubmed
    ..1 channel. Such stronger inhibition by the open form of Syn-1A may limit K+ efflux and thus decelerate membrane repolarization during exocytosis, leading to optimization of insulin release. ..
  47. Shen J, Rathore S, Khandan L, Rothman J. SNARE bundle and syntaxin N-peptide constitute a minimal complement for Munc18-1 activation of membrane fusion. J Cell Biol. 2010;190:55-63 pubmed publisher
    ..The synaptic target membrane SNARE syntaxin 1 contains a highly conserved H(abc) domain, which connects an N-peptide motif to the SNARE core domain and is ..
  48. Condliffe S, Carattino M, Frizzell R, Zhang H. Syntaxin 1A regulates ENaC via domain-specific interactions. J Biol Chem. 2003;278:12796-804 pubmed
    ..This study provides support for the concept that S1A inhibits ENaC-mediated Na(+) transport by decreasing cell surface channel number via direct protein-protein interactions at the ENaC C termini. ..
  49. Kümmel D, Krishnakumar S, Radoff D, Li F, Giraudo C, Pincet F, et al. Complexin cross-links prefusion SNAREs into a zigzag array. Nat Struct Mol Biol. 2011;18:927-33 pubmed publisher
    ..Thus, complexin organizes the SNAREs into a zigzag topology that, when interposed between the vesicle and plasma membranes, is incompatible with fusion. ..
  50. Castillo M, Ghose S, Tamminga C, Ulery Reynolds P. Deficits in syntaxin 1 phosphorylation in schizophrenia prefrontal cortex. Biol Psychiatry. 2010;67:208-16 pubmed publisher
    ..of subjects with schizophrenia, we hypothesized that CK2-mediated phosphorylation of the presynaptic protein syntaxin 1 (Stx 1) is deficient in schizophrenia...
  51. Constable J, Graham M, Morgan A, Burgoyne R. Amisyn regulates exocytosis and fusion pore stability by both syntaxin-dependent and syntaxin-independent mechanisms. J Biol Chem. 2005;280:31615-23 pubmed the possession of a C-terminal vesicle-associated membrane protein-like domain that allows them to bind to syntaxin 1 and assemble into SNARE complexes...
  52. Holt M, Riedel D, Stein A, Schuette C, Jahn R. Synaptic vesicles are constitutively active fusion machines that function independently of Ca2+. Curr Biol. 2008;18:715-722 pubmed publisher
    ..Many proteins required for this process have been identified, with the SNAREs syntaxin 1, SNAP-25, and synaptobrevin thought to constitute the core fusion machinery...
  53. Bajohrs M, Rickman C, Binz T, Davletov B. A molecular basis underlying differences in the toxicity of botulinum serotypes A and E. EMBO Rep. 2004;5:1090-5 pubmed