Stxbp1

Summary

Gene Symbol: Stxbp1
Description: syntaxin binding protein 1
Alias: ANC18HA, Munc18-1, NSEC1A, Sec1, Unc18-1, n-sec1, nSec1, rbSec1, rbSec1A, rbSec1B, syntaxin-binding protein 1, p67, protein unc-18 homolog 1, protein unc-18 homolog A, unc-18 homolog, unc-18-1, unc-18A
Species: rat
Products:     Stxbp1

Top Publications

  1. Han L, Jiang T, Han G, Malintan N, Xie L, Wang L, et al. Rescue of Munc18-1 and -2 double knockdown reveals the essential functions of interaction between Munc18 and closed syntaxin in PC12 cells. Mol Biol Cell. 2009;20:4962-75 pubmed publisher
    ..Our studies also indicate that the binding to the closed conformation of syntaxin is essential for Munc18-1 stimulatory action, whereas the binding to syntaxin N terminus plays a more limited role in neurosecretory cells. ..
  2. Hata Y, Sudhof T. 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. 1995;270:13022-8 pubmed
    ..The lack of specificity of the interactions between syntaxins and Munc-18s indicates that specificity of membrane trafficking reactions is not dependent on this interaction. ..
  3. Zilly F, Sørensen J, Jahn R, Lang T. Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes. PLoS Biol. 2006;4:e330 pubmed
    Munc18-1, a protein essential for regulated exocytosis in neurons and neuroendocrine cells, belongs to the family of Sec1/Munc18-like (SM) proteins...
  4. Okamoto M, Sudhof T. Mints, Munc18-interacting proteins in synaptic vesicle exocytosis. J Biol Chem. 1997;272:31459-64 pubmed
    ..F. J. (1995) Nature 374, 173-177). Our data suggest a model whereby local production of phosphatidylinositol phosphates may trigger the binding of vesicles to the active zone via the Mint.Munc18-1 complex in conjunction with syntaxin 1. ..
  5. Burkhardt P, Hattendorf D, Weis W, Fasshauer D. Munc18a controls SNARE assembly through its interaction with the syntaxin N-peptide. EMBO J. 2008;27:923-33 pubmed publisher
    b>Sec1/Munc18-like (SM) proteins functionally interact with SNARE proteins in vesicular fusion. Despite their high sequence conservation, structurally disparate binding modes for SM proteins with syntaxins have been observed...
  6. 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. ..
  7. Pevsner J, Hsu S, Scheller R. n-Sec1: a neural-specific syntaxin-binding protein. Proc Natl Acad Sci U S A. 1994;91:1445-9 pubmed
    We have identified n-Sec1, a rat brain homolog of the yeast Sec1p protein that participates in the constitutive secretory pathway between the Golgi apparatus and the plasma membrane...
  8. 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/nSec1, a synaptic SM protein required for neurotransmitter release, strongly accelerates this reaction through direct ..
  9. Hata Y, Slaughter C, Sudhof T. Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin. Nature. 1993;366:347-51 pubmed
    ..Our data suggest that Munc-18 is a previously unidentified essential component of the synaptic vesicle fusion protein complex. ..

More Information

Publications62

  1. Fujita Y, Sasaki T, Fukui K, Kotani H, Kimura T, Hata Y, et al. Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C: its implication in regulating the interaction of Munc-18/n-Sec1/rbSec1 with syntaxin. J Biol Chem. 1996;271:7265-8 pubmed
    Munc-18/n-Sec1/rbSec1 interacts with syntaxin and this interaction inhibits the association of vesicle-associated membrane protein (VAMP)/synaptobrevin and synaptosomal-associated protein of 25 kDa (SNAP-25) with syntaxin...
  2. Misura K, Scheller R, Weis W. Three-dimensional structure of the neuronal-Sec1-syntaxin 1a complex. Nature. 2000;404:355-62 pubmed
    Syntaxin 1a and neuronal Sec1 (nSec1) form an evolutionarily conserved heterodimer that is essential for vesicle trafficking and membrane fusion. The crystal structure of the nSec1-syntaxin 1a complex, determined at 2...
  3. Smyth A, Yang L, Martin K, Hamilton C, Lu W, Cousin M, et al. Munc18-1 protein molecules move between membrane molecular depots distinct from vesicle docking sites. J Biol Chem. 2013;288:5102-13 pubmed publisher
    ..Our findings demonstrate that Munc18-1 molecules move between membrane depots distinct from vesicle morphological docking sites. ..
  4. Guan R, Dai H, Rizo J. Binding of the Munc13-1 MUN domain to membrane-anchored SNARE complexes. Biochemistry. 2008;47:1474-81 pubmed publisher
  5. 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
  6. Voets T, Toonen R, Brian E, de Wit H, Moser T, Rettig J, et al. Munc18-1 promotes large dense-core vesicle docking. Neuron. 2001;31:581-91 pubmed
    ..We conclude that Munc18-1 functions upstream of SNARE complex formation and promotes LDCV docking. ..
  7. Rickman C, Duncan R. Munc18/Syntaxin interaction kinetics control secretory vesicle dynamics. J Biol Chem. 2010;285:3965-72 pubmed publisher
    ..Destabilization of this dynamic interaction enhanced vesicle immobilization at the plasma membrane with a resulting inhibition of exocytosis. ..
  8. Dulubova I, Yamaguchi T, Arac D, Li H, Huryeva I, Min S, et al. Convergence and divergence in the mechanism of SNARE binding by Sec1/Munc18-like proteins. Proc Natl Acad Sci U S A. 2003;100:32-7 pubmed
  9. Malintan N, Nguyen T, Han L, Latham C, Osborne S, Wen P, et al. Abrogating Munc18-1-SNARE complex interaction has limited impact on exocytosis in PC12 cells. J Biol Chem. 2009;284:21637-46 pubmed publisher
    ..proteins initiate membrane fusion through the formation of the SNARE complex, a process tightly regulated by Sec1/Munc18-1 (SM) proteins...
  10. Deak F, Xu Y, Chang W, Dulubova I, Khvotchev M, Liu X, et al. Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming. J Cell Biol. 2009;184:751-64 pubmed publisher
  11. Rodkey T, Liu S, Barry M, McNew J. Munc18a scaffolds SNARE assembly to promote membrane fusion. Mol Biol Cell. 2008;19:5422-34 pubmed publisher
    ..In this capacity, Munc18a serves as a platform for trans-SNARE complex assembly that facilitates efficient SNARE-mediated membrane fusion. ..
  12. Graham M, Barclay J, Burgoyne R. Syntaxin/Munc18 interactions in the late events during vesicle fusion and release in exocytosis. J Biol Chem. 2004;279:32751-60 pubmed
    ..for the speed, spatial restriction, and tight control of exocytosis and a key role is played by members of the Sec1/Munc18 family of proteins that have been implicated either in vesicle docking or fusion itself through their ..
  13. Dulubova I, Khvotchev M, Liu S, Huryeva I, Sudhof T, Rizo J. Munc18-1 binds directly to the neuronal SNARE complex. Proc Natl Acad Sci U S A. 2007;104:2697-702 pubmed
    Both SM proteins (for Sec1/Munc18-like proteins) and SNARE proteins (for soluble NSF-attachment protein receptors) are essential for intracellular membrane fusion, but the general mechanism of coupling between their functions is unclear, ..
  14. 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. ..
  15. Garcia E, Gatti E, Butler M, Burton J, De Camilli P. A rat brain Sec1 homologue related to Rop and UNC18 interacts with syntaxin. Proc Natl Acad Sci U S A. 1994;91:2003-7 pubmed
    ..5-kb brain-specific mRNA by Northern blot analysis and encodes a protein of 593 amino acids (rbSec1). Antibodies raised against a central portion of rbSec1 recognize a 67...
  16. Katagiri H, Terasaki J, Murata T, Ishihara H, Ogihara T, Inukai K, et al. A novel isoform of syntaxin-binding protein homologous to yeast Sec1 expressed ubiquitously in mammalian cells. J Biol Chem. 1995;270:4963-6 pubmed
    munc-18/n-Sec1/rbSec1, a brain homologue of the yeast Sec1p protein, is thought to participate in regulating the docking and fusion of synaptic vesicles...
  17. Smyth A, Rickman C, Duncan R. Vesicle fusion probability is determined by the specific interactions of munc18. J Biol Chem. 2010;285:38141-8 pubmed publisher
    ..We therefore conclude that interaction with the syntaxin N-peptide can confer differential release probabilities to secretory vesicles and may contribute to the delineation of secretory vesicle pools. ..
  18. Lou X, Shin J, Yang Y, Kim J, Shin Y. Synaptotagmin-1 is an antagonist for Munc18-1 in SNARE zippering. J Biol Chem. 2015;290:10535-43 pubmed publisher
    ..of a major Ca(2+) sensor synaptotagmin-1 (Syt1), providing the structural basis for the conserved function of Sec1/Munc18 proteins in exocytosis...
  19. Zhang Y, Wan P, Wang H, Zhao H, Xu Y, Yang R, et al. Effect of neuronal excitotoxicity on Munc18-1 distribution in nuclei of rat hippocampal neuron and primary cultured neuron. Neurosci Bull. 2011;27:163-72 pubmed publisher
    ..These results suggest that excitatory stimulation can induce the distribution change of Munc18-1 in neuron, which may subsequently modulate neuronal functions in brain. ..
  20. Cao F, Hata R, Zhu P, Niinobe M, Sakanaka M. Up-regulation of syntaxin1 in ischemic cortex after permanent focal ischemia in rats. Brain Res. 2009;1272:52-61 pubmed publisher
    ..Furthermore, we showed that resident microglial cells were quite vulnerable to ischemia. Our data provide novel insights into the molecular mechanism of cerebral ischemia at the pre-synaptic terminals. ..
  21. Pertsinidis A, Mukherjee K, Sharma M, Pang Z, Park S, Zhang Y, et al. Ultrahigh-resolution imaging reveals formation of neuronal SNARE/Munc18 complexes in situ. Proc Natl Acad Sci U S A. 2013;110:E2812-20 pubmed publisher
    Membrane fusion is mediated by complexes formed by SNAP-receptor (SNARE) and Secretory 1 (Sec1)/mammalian uncoordinated-18 (Munc18)-like (SM) proteins, but it is unclear when and how these complexes assemble...
  22. Ho A, Morishita W, Atasoy D, Liu X, Tabuchi K, Hammer R, et al. Genetic analysis of Mint/X11 proteins: essential presynaptic functions of a neuronal adaptor protein family. J Neurosci. 2006;26:13089-101 pubmed
    ..Our studies thus indicate that Mints are important regulators of presynaptic neurotransmitter release that are essential for mouse survival. ..
  23. Sharma V, Shareef M, Bhaskar K, Kalidas S, Shetty P, Christopher R, et al. Nuclear localization of Munc18-1 (p67) in the adult rat brain and PC12 cells. Neurochem Int. 2005;47:225-34 pubmed
    Munc18-1, also referred to as p67, co-purifies with Cdk5 and has an important role in neurotransmitter release...
  24. Heeroma J, Roelandse M, Wierda K, van Aerde K, Toonen R, Hensbroek R, et al. Trophic support delays but does not prevent cell-intrinsic degeneration of neurons deficient for munc18-1. Eur J Neurosci. 2004;20:623-34 pubmed
    ..Second, trophic support delays but cannot prevent degeneration. Third, a cell-intrinsic yet unknown function of munc18-1 is essential for prolonged survival. ..
  25. Lilja L, Johansson J, Gromada J, Mandic S, Fried G, Berggren P, et al. Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca(2+)-dependent exocytosis. J Biol Chem. 2004;279:29534-41 pubmed
  26. Bhaskar K, Shareef M, Sharma V, Shetty A, Ramamohan Y, Pant H, et al. Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins. Neurochem Int. 2004;44:35-44 pubmed
    Munc18-1 (p67, nSec1, rbSec1), a neuron-specific 67kDa protein was independently identified as a syntaxin-binding protein, and as a component that co-purifies with, and regulates the kinase activity of cyclin dependent kinase (Cdk5)...
  27. Schraw T, Lemons P, Dean W, Whiteheart S. A role for Sec1/Munc18 proteins in platelet exocytosis. Biochem J. 2003;374:207-17 pubmed publisher
    ..Three Sec1/Munc18 proteins (SM proteins) are present in platelets (Munc18a, Munc18b and Munc18c) and they bind to and ..
  28. Perez Branguli F, Muhaisen A, Blasi J. 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. 2002;20:169-80 pubmed
    ..Since Munc-18a can bind both isoforms of syntaxin 1, the present data suggest that this protein is a general modulator of the formation of different SNARE complexes in the nerve endings. ..
  29. Chai Y, Sierecki E, Tomatis V, Gormal R, Giles N, Morrow I, et al. Munc18-1 is a molecular chaperone for α-synuclein, controlling its self-replicating aggregation. J Cell Biol. 2016;214:705-18 pubmed publisher
  30. Arnold M, Adhikari P, Kang B, Xu 徐昊 H. Munc18a clusters SNARE-bearing liposomes prior to trans-SNARE zippering. Biochem J. 2017;474:3339-3354 pubmed publisher
    ..Studies of Munc18a/Munc18-1/Stxbp1 in neurotransmission suggest that SM proteins accelerate fusion kinetics primarily by activating the partially ..
  31. Lam P, Hyvärinen K, Kauppi M, Cosen Binker L, Laitinen S, Keränen S, et al. A cytosolic splice variant of Cab45 interacts with Munc18b and impacts on amylase secretion by pancreatic acini. Mol Biol Cell. 2007;18:2473-80 pubmed
    ..The present study identifies Cab45b as a novel protein factor involved in the exocytosis of zymogens by pancreatic acini. ..
  32. Weckhuysen S, Holmgren P, Hendrickx R, Jansen A, Hasaerts D, Dielman C, et al. Reduction of seizure frequency after epilepsy surgery in a patient with STXBP1 encephalopathy and clinical description of six novel mutation carriers. Epilepsia. 2013;54:e74-80 pubmed publisher
    Mutations in STXBP1 have been identified in a subset of patients with early onset epileptic encephalopathy (EE), but the full phenotypic spectrum remains to be delineated...
  33. Zhang Y, Diao J, Colbert K, Lai Y, Pfuetzner R, Padolina M, et al. Munc18a does not alter fusion rates mediated by neuronal SNAREs, synaptotagmin, and complexin. J Biol Chem. 2015;290:10518-34 pubmed publisher
    ..with reconstituted neuronal SNAREs, synaptotagmin-1, and complexin-1, we show that the neuronal SM protein Munc18a/nSec1 has no effect on the intrinsic kinetics of both spontaneous fusion and Ca(2+)-triggered fusion between vesicles ..
  34. Kim B, Choi J, Ahn K, Jeong J, Ha C, Jeong C, et al. Munc18 plays an important role in the regulation of glutamate release during female puberty onset. Mol Cells. 2006;22:30-5 pubmed
    ..These results suggest that Munc18-1, expressed in an estrogen-dependent manner, plays an important role in the onset of female puberty via the regulation of glutamate release. ..
  35. Garcia E, McPherson P, Chilcote T, Takei K, De Camilli P. rbSec1A and B colocalize with syntaxin 1 and SNAP-25 throughout the axon, but are not in a stable complex with syntaxin. J Cell Biol. 1995;129:105-20 pubmed
    ..rbSec1, which we show here to be represented by two alternatively spliced isoforms, rbSec1A and B, has a widespread distribution in the axon and is not restricted to the nerve terminal...
  36. Kavanagh D, Smyth A, Martin K, Dun A, Brown E, Gordon S, et al. A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion. Nat Commun. 2014;5:5774 pubmed publisher
  37. Saitsu H, Kato M, Mizuguchi T, Hamada K, Osaka H, Tohyama J, et al. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet. 2008;40:782-8 pubmed publisher
    ..that four unrelated individuals with EIEE had heterozygous missense mutations in the gene encoding syntaxin binding protein 1 (STXBP1)...
  38. Deprez L, Weckhuysen S, Holmgren P, Suls A, Van Dyck T, Goossens D, et al. Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. Neurology. 2010;75:1159-65 pubmed publisher
    Heterozygous mutations in STXBP1, encoding the syntaxin binding protein 1, have recently been identified in Ohtahara syndrome, an epileptic encephalopathy with very early onset...
  39. Martin S, Tomatis V, Papadopulos A, Christie M, Malintan N, Gormal R, et al. The Munc18-1 domain 3a loop is essential for neuroexocytosis but not for syntaxin-1A transport to the plasma membrane. J Cell Sci. 2013;126:2353-60 pubmed publisher
    ..Together, these results point to a defined role for Munc18-1 in facilitating exocytosis linked to the loop region of domain 3a that is clearly distinct from its function in Sx1a transport. ..
  40. Shetty K, Kaech S, Link W, Jaffe H, Flores C, Wray S, et al. Molecular characterization of a neuronal-specific protein that stimulates the activity of Cdk5. J Neurochem. 1995;64:1988-95 pubmed
    ..A single full-length cDNA was characterized coding for a 67.5-kDa protein (p67)...
  41. Matsuo N, Ogawa S, Takagi T, Wanaka A, Mori T, Matsuyama T, et al. Cloning of a putative vesicle transport-related protein, RA410, from cultured rat astrocytes and its expression in ischemic rat brain. J Biol Chem. 1997;272:16438-44 pubmed
    ..amino acid sequence showed RA410 to be composed of domains common to vesicle transport-related proteins of the Sec1/Unc18 family, including Sly1p and Sec1p (yeast), Rop (Drosophila), Unc18 (Caenorhabditis elegans), and Munc18 (..
  42. Dawidowski D, Cafiso D. Munc18-1 and the Syntaxin-1 N Terminus Regulate Open-Closed States in a t-SNARE Complex. Structure. 2016;24:392-400 pubmed publisher
  43. Tian J, Das S, Sheng Z. Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18. J Biol Chem. 2003;278:26265-74 pubmed
    ..Our results suggest that syntaxin is a DAP kinase substrate and provide a novel signal transduction pathway by which syntaxin function could be regulated in response to intracellular [Ca2+] and synaptic activity. ..
  44. Lim S, Moon J, Lee M, Lee J. PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1 through dephosphorylation of specific tyrosine residue. Biochem Biophys Res Commun. 2013;439:40-6 pubmed publisher
    ..In conclusion, PTPRT could regulate the interaction of Syntaxin-binding protein 1 with Syntaxin 1, and as a result, the synaptic vesicle fusion appeared to be controlled through dephosphorylation of Syntaxin-binding protein 1. ..
  45. Dong Y, Wan Q, Yang X, Bai L, Xu P. Interaction of Munc18 and Syntaxin in the regulation of insulin secretion. Biochem Biophys Res Commun. 2007;360:609-14 pubmed
    ..We propose that Munc18-1 inhibitis the SNARE complex assembly by stabilizing Syntaxin1A in a closed conformation in vesicle priming process, therefore negatively regulates insulin secretion. ..
  46. Toonen R, Wierda K, Sons M, de Wit H, Cornelisse L, Brussaard A, et al. Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size. Proc Natl Acad Sci U S A. 2006;103:18332-7 pubmed
    ..These data show that varying expression of a single gene controls synaptic recovery by modulating the number of docked, release-ready vesicles and thereby replenishment of the secretion capacity. ..
  47. Ciufo L, Barclay J, Burgoyne R, Morgan A. Munc18-1 regulates early and late stages of exocytosis via syntaxin-independent protein interactions. Mol Biol Cell. 2005;16:470-82 pubmed
    b>Sec1/Munc18 (SM) proteins are involved in various intracellular membrane trafficking steps. Many SM proteins bind to appropriate syntaxin homologues involved in these steps, suggesting that SM proteins function as syntaxin chaperones...
  48. Biederer T, Sudhof T. Mints as adaptors. Direct binding to neurexins and recruitment of munc18. J Biol Chem. 2000;275:39803-6 pubmed
    Mint1 (X11/human Lin-10) and Mint2 are neuronal adaptor proteins that bind to Munc18-1 (n/rb-sec1), a protein essential for synaptic vesicle exocytosis...
  49. Shi L, Kümmel D, Coleman J, Melia T, Giraudo C. Dual roles of Munc18-1 rely on distinct binding modes of the central cavity with Stx1A and SNARE complex. Mol Biol Cell. 2011;22:4150-60 pubmed publisher
    b>Sec1/Munc18 proteins play a fundamental role in multiple steps of intracellular membrane trafficking...
  50. Nakajima Y, Mochida S, Okawa K, Nakanishi S. Ca2+-dependent release of Munc18-1 from presynaptic mGluRs in short-term facilitation. Proc Natl Acad Sci U S A. 2009;106:18385-9 pubmed publisher
    ..Here, we show that presynaptic metabotropic glutamate receptors (mGluRs) bind and release Munc18-1 (also known as rbSec1/nSec1), an essential protein for synaptic transmission, in a Ca(2+)-dependent manner, whose actions decrease and ..
  51. Ma C, Su L, Seven A, Xu Y, Rizo J. Reconstitution of the vital functions of Munc18 and Munc13 in neurotransmitter release. Science. 2013;339:421-5 pubmed publisher
  52. Coppola T, Frantz C, Perret Menoud V, Gattesco S, Hirling H, Regazzi R. Pancreatic beta-cell protein granuphilin binds Rab3 and Munc-18 and controls exocytosis. Mol Biol Cell. 2002;13:1906-15 pubmed
    ..In view of the postulated role of Munc-18 in secretory vesicle docking, our data suggest that granuphilins may also be involved in this process. ..
  53. Dai X, Plummer G, Casimir M, Kang Y, Hajmrle C, Gaisano H, et al. SUMOylation regulates insulin exocytosis downstream of secretory granule docking in rodents and humans. Diabetes. 2011;60:838-47 pubmed publisher
    ..SUMOylation acutely regulates insulin secretion by the direct and reversible inhibition of ?-cell exocytosis in response to intracellular Ca(2+) elevation. The SUMO protease, SENP1, is required for glucose-dependent insulin secretion. ..