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Gene Review

Stxbp1  -  syntaxin binding protein 1

Mus musculus

Synonyms: AI317162, AI326233, MMS10-G, Ms10g, Munc-18a, ...
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Disease relevance of Stxbp1

  • A pulsed KTP pumped dye laser (25 kHz repetition rate and 470 nsec pulse width) has been compared to a continuous wave argon ion pumped dye laser as the source of 630 nm light during in-vitro and in-vivo Photofrin-II mediated photosensitization studies [1].

High impact information on Stxbp1

  • Deletion of a single protein, Munc18-1, in mice leads to a complete loss of neurotransmitter secretion from synaptic vesicles throughout development [2].
  • Calcium-dependent LDCV exocytosis was reduced 10-fold in mouse chromaffin cells lacking Munc18-1, but the kinetic properties of the remaining release, including single fusion events, were not different from controls [3].
  • Munc18-1 promotes large dense-core vesicle docking [3].
  • Moreover, acute overexpression of Munc18-1 in bovine chromaffin cells increased the amount of releasable vesicles and accelerated vesicle supply [3].
  • To determine the role of n-Sec1/Munc-18 in neurotransmitter release in vivo, we have overexpressed the Drosophila homolog, rop, in third instar larvae and measured the electrophysiological consequences at the neuromuscular junction [4].

Biological context of Stxbp1


Anatomical context of Stxbp1

  • This implicates the existence of other mammalian Munc-18 homologues that may be involved in a range of vesicle transport reactions [10].
  • Munc-18a is identical to Munc-18 and by Northern analysis is expressed predominantly in brain and to a lesser extent in testis and 3T3-L1 cells [10].
  • We have previously identified three mammalian Sec1/Munc-18 homologues in adipocytes (Tellam, J. T., McIntosh, S., and James, D. E. (1995) J. Biol. Chem. 270, 5857-5863) [11].
  • Expression of Munc13-1, along with its cognate partners, syntaxin 1a and Munc18a, is reduced in the pancreatic islets of type-2 diabetes non-obese Goto-Kakizaki and obese Zucker fa/fa rats [12].
  • Here, we report on our investigation of the role of syntaxin-binding Munc18 isoforms and the microtubule network in this process [13].

Associations of Stxbp1 with chemical compounds

  • The present study provides supporting evidence for the involvement of Stxbp1 in ethanol preference drinking [5].
  • These data suggest that Munc-18-1 and C. elegans unc-18 may play positive roles in ACh release and that the molecular mechanism of neuronal regulated secretion has been partially conserved from nematodes to mammals [9].

Enzymatic interactions of Stxbp1

  • We have now demonstrated that Cdk5 is capable of phosphorylating Munc18a in vitro within a preformed Munc18a.syntaxin 1a heterodimer complex and that this results in the disassembly of the complex [6].

Regulatory relationships of Stxbp1


Other interactions of Stxbp1

  • Munc-18c is 51% identical to Munc-18 and is ubiquitously expressed [10].
  • Munc-18b is 62% identical to Munc-18 at the amino acid level and is expressed in testis, intestine, kidney, rat adipose tissue, and 3T3-L1 cells [10].
  • The enhanced secretion in mutant beta cells is correlated with a decrease in the formation of the fusion-incompetent syntaxin-1a-Munc18-1 complex, with which granuphilin normally interacts [15].
  • As such, regulation of the interaction between Munc18a and syntaxin 1a may provide an important mechanism controlling secretory responsiveness [6].
  • Three SM (Sec1/Munc18) proteins are present in mouse platelets (Munc18a, 18b and 18c) and each potentially regulates exocytosis via modulation of their cognate syntaxin binding partner [16].

Analytical, diagnostic and therapeutic context of Stxbp1


  1. Direct comparison of in-vitro and in-vivo Photofrin-II mediated photosensitization using a pulsed KTP pumped dye laser and a continuous wave argon ion pumped dye laser. Ferrario, A., Rucker, N., Ryter, S.W., Doiron, D.R., Gomer, C.J. Lasers in surgery and medicine. (1991) [Pubmed]
  2. Synaptic assembly of the brain in the absence of neurotransmitter secretion. Verhage, M., Maia, A.S., Plomp, J.J., Brussaard, A.B., Heeroma, J.H., Vermeer, H., Toonen, R.F., Hammer, R.E., van den Berg, T.K., Missler, M., Geuze, H.J., Südhof, T.C. Science (2000) [Pubmed]
  3. Munc18-1 promotes large dense-core vesicle docking. Voets, T., Toonen, R.F., Brian, E.C., de Wit, H., Moser, T., Rettig, J., Südhof, T.C., Neher, E., Verhage, M. Neuron (2001) [Pubmed]
  4. rop, a Drosophila homolog of yeast Sec1 and vertebrate n-Sec1/Munc-18 proteins, is a negative regulator of neurotransmitter release in vivo. Schulze, K.L., Littleton, J.T., Salzberg, A., Halachmi, N., Stern, M., Lev, Z., Bellen, H.J. Neuron (1994) [Pubmed]
  5. The syntaxin binding protein 1 gene (Stxbp1) is a candidate for an ethanol preference drinking locus on mouse chromosome 2. Fehr, C., Shirley, R.L., Crabbe, J.C., Belknap, J.K., Buck, K.J., Phillips, T.J. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  6. Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18. Fletcher, A.I., Shuang, R., Giovannucci, D.R., Zhang, L., Bittner, M.A., Stuenkel, E.L. J. Biol. Chem. (1999) [Pubmed]
  7. Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation. Toonen, R.F., de Vries, K.J., Zalm, R., Südhof, T.C., Verhage, M. J. Neurochem. (2005) [Pubmed]
  8. Gene structure and promoter function of murine Munc18-2, a nonneuronal exocytic Sec1 homolog. Agrawal, A., Adachi, R., Tuvim, M., Yan, X.T., Teich, A.H., Dickey, B.F. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  9. A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants. Gengyo-Ando, K., Kitayama, H., Mukaida, M., Ikawa, Y. J. Neurosci. (1996) [Pubmed]
  10. Molecular identification of two novel Munc-18 isoforms expressed in non-neuronal tissues. Tellam, J.T., McIntosh, S., James, D.E. J. Biol. Chem. (1995) [Pubmed]
  11. Characterization of Munc-18c and syntaxin-4 in 3T3-L1 adipocytes. Putative role in insulin-dependent movement of GLUT-4. Tellam, J.T., Macaulay, S.L., McIntosh, S., Hewish, D.R., Ward, C.W., James, D.E. J. Biol. Chem. (1997) [Pubmed]
  12. Regulation of insulin exocytosis by Munc13-1. Sheu, L., Pasyk, E.A., Ji, J., Huang, X., Gao, X., Varoqueaux, F., Brose, N., Gaisano, H.Y. J. Biol. Chem. (2003) [Pubmed]
  13. Evidence of a role for Munc18-2 and microtubules in mast cell granule exocytosis. Martin-Verdeaux, S., Pombo, I., Iannascoli, B., Roa, M., Varin-Blank, N., Rivera, J., Blank, U. J. Cell. Sci. (2003) [Pubmed]
  14. Two distinct genes drive expression of seven tomosyn isoforms in the mammalian brain, sharing a conserved structure with a unique variable domain. Groffen, A.J., Jacobsen, L., Schut, D., Verhage, M. J. Neurochem. (2005) [Pubmed]
  15. Granuphilin molecularly docks insulin granules to the fusion machinery. Gomi, H., Mizutani, S., Kasai, K., Itohara, S., Izumi, T. J. Cell Biol. (2005) [Pubmed]
  16. Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release. Schraw, T.D., Crawford, G.L., Ren, Q., Choi, W., Thurmond, D.C., Pessin, J., Whiteheart, S.W. Thromb. Haemost. (2004) [Pubmed]
  17. Munc18-syntaxin complexes and exocytosis in human platelets. Houng, A., Polgar, J., Reed, G.L. J. Biol. Chem. (2003) [Pubmed]
  18. Slp4-a/granuphilin-a inhibits dense-core vesicle exocytosis through interaction with the GDP-bound form of Rab27A in PC12 cells. Fukuda, M. J. Biol. Chem. (2003) [Pubmed]
  19. Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl- and N-tert-alkylnormorphines. DeGraw, J.I., Lawson, J.A., Crase, J.L., Johnson, H.L., Ellis, M., Uyeno, E.T., Loew, G.H., Berkowitz, D.S. J. Med. Chem. (1978) [Pubmed]
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