Gene Symbol: Stxbp1
Description: syntaxin binding protein 1
Alias: AI317162, AI326233, MMS10-G, Ms10g, Munc-18a, Munc18-1, N-sec1, Rb-sec1, Sxtbp1, Unc18-1, Unc18h, nsec1, syntaxin-binding protein 1, UNC-18 homolog, minisatellite 10g detected by probe MMS10, protein unc-18 homolog 1, protein unc-18 homolog A, unc-18-1, unc-18A
Species: mouse
Products:     Stxbp1

Top Publications

  1. Toonen R, Kochubey O, de Wit H, Gulyas Kovacs A, Konijnenburg B, Sørensen J, et al. Dissecting docking and tethering of secretory vesicles at the target membrane. EMBO J. 2006;25:3725-37 pubmed
    ..We conclude that docking vesicles either undock immediately or are captured by minimal tethering machinery and converted in a munc18-1/syntaxin-dependent, strongly tethered, fusion-competent state. ..
  2. 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
    ..Our superresolution imaging method provides a framework for investigating interactions between the synaptic vesicle fusion machinery and other subcellular systems in situ. ..
  3. de Wit H, Walter A, Milosevic I, Gulyas Kovacs A, Riedel D, Sørensen J, et al. Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes. Cell. 2009;138:935-46 pubmed publisher
  4. 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. ..
  5. Wierda K, Toonen R, de Wit H, Brussaard A, Verhage M. Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity. Neuron. 2007;54:275-90 pubmed
    ..Munc18-1 is an essential downstream target in the PKC pathway. This pathway is of general importance for presynaptic plasticity. ..
  6. 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. ..
  7. Bouwman J, Maia A, Camoletto P, Posthuma G, Roubos E, Oorschot V, et al. Quantification of synapse formation and maintenance in vivo in the absence of synaptic release. Neuroscience. 2004;126:115-26 pubmed
    ..These two observations suggest that secretion of neurotransmitters and neuromodulatory substances is required for synapse maintenance, not for synaptogenesis. Multivesicular structures may develop out of unstable synapses. ..
  8. Tellam J, McIntosh S, James D. Molecular identification of two novel Munc-18 isoforms expressed in non-neuronal tissues. J Biol Chem. 1995;270:5857-63 pubmed
    ..It is likely, based on these findings, that unique Munc-18/syntaxin interactions may play an important role in generating a combinatorial mechanism for the regulation of vesicle transport in mammalian cells. ..
  9. 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
    ..Thus, the SNARE four-helix bundle and syntaxin N-peptide constitute a minimal complement for Munc18-1 activation of fusion. ..

More Information


  1. Broeke J, Roelandse M, Luteijn M, Boiko T, Matus A, Toonen R, et al. Munc18 and Munc13 regulate early neurite outgrowth. Biol Cell. 2010;102:479-88 pubmed publisher
    ..In addition, Munc18, but not Munc13, regulates growth cone filopodia, potentially via its previously observed effect on filamentous actin. ..
  2. 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
  3. Korteweg N, Maia A, Verhage M, Burbach J. Development of the mouse hypothalamo-neurohypophysial system in the munc18-1 null mutant that lacks regulated secretion. Eur J Neurosci. 2004;19:2944-52 pubmed
    ..Thus, the communication between the outgrowing neurons and the pituicytes could serve to integrate these two cell types to constitute a functional peptidergic system. ..
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. Verhage M, Maia A, Plomp J, Brussaard A, Heeroma J, Vermeer H, et al. Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science. 2000;287:864-9 pubmed
    ..Thus, synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does. Neurotransmitter secretion probably functions to validate already established synaptic connections. ..
  8. Heeroma J, Plomp J, Roubos E, Verhage M. Development of the mouse neuromuscular junction in the absence of regulated secretion. Neuroscience. 2003;120:733-44 pubmed
    ..However, in the absence of regulated secretion, the maintenance of the motor neuronal system, organization of nerve terminal branches and stabilization of synapses is impaired and a-neural postsynaptic elements persist. ..
  9. Ramos Miguel A, Hercher C, Beasley C, Barr A, Bayer T, Falkai P, et al. Loss of Munc18-1 long splice variant in GABAergic terminals is associated with cognitive decline and increased risk of dementia in a community sample. Mol Neurodegener. 2015;10:65 pubmed publisher
    ..Lower M18L in inhibitory presynaptic terminals may be an early, independent contributor to cognitive decline. ..
  10. Jewell J, Oh E, Thurmond D. Exocytosis mechanisms underlying insulin release and glucose uptake: conserved roles for Munc18c and syntaxin 4. Am J Physiol Regul Integr Comp Physiol. 2010;298:R517-31 pubmed publisher
    ..Thus, we provide here an up-to-date historical review of advancements in defining the roles and molecular mechanisms of Munc18-syntaxin complexes in the pathophysiology of Type 2 diabetes. ..
  11. 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
    ..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 ..
  12. Gotoh K, Yokota H, Kikuya E, Watanabe T, Oishi M. Genomic structure of MUNC18-1 protein, which is involved in docking and fusion of synaptic vesicles in brain. J Biol Chem. 1998;273:21642-7 pubmed
    ..Transfection experiments employing these and upstream sequences suggest the presence of a sequence(s) that negatively regulates the expression of munc18-1 gene. ..
  13. Oh E, Kalwat M, Kim M, Verhage M, Thurmond D. Munc18-1 regulates first-phase insulin release by promoting granule docking to multiple syntaxin isoforms. J Biol Chem. 2012;287:25821-33 pubmed publisher
    ..Given that Munc18-1 does not pair with syntaxin 4, these data suggest a novel indirect role for Munc18-1 in facilitating syntaxin 4-mediated granule pre-docking to support first-phase insulin exocytosis...
  14. Gengyo Ando K, Kitayama H, Mukaida M, Ikawa Y. A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants. J Neurosci. 1996;16:6695-702 pubmed
    ..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. ..
  15. Sakane A, Manabe S, Ishizaki H, Tanaka Okamoto M, Kiyokage E, Toida K, et al. Rab3 GTPase-activating protein regulates synaptic transmission and plasticity through the inactivation of Rab3. Proc Natl Acad Sci U S A. 2006;103:10029-34 pubmed
    ..Thus, Rab3 GAP regulates synaptic transmission and plasticity by limiting the amount of the GTP-bound form of Rab3A. ..
  16. Korteweg N, Maia A, Thompson B, Roubos E, Burbach J, Verhage M. The role of Munc18-1 in docking and exocytosis of peptide hormone vesicles in the anterior pituitary. Biol Cell. 2005;97:445-55 pubmed
    ..2000). We conclude that Munc18-1 is involved in the secretion of peptide hormones and in the docking of LDCVs. These results unmask an apparent mechanistic difference between LDCVs and synaptic vesicles. ..
  17. Ha H, Cho I, Lee K, Lee K, Song J, Kim K, et al. The axon guidance defect of the telencephalic commissures of the JSAP1-deficient brain was partially rescued by the transgenic expression of JIP1. Dev Biol. 2005;277:184-99 pubmed
  18. Cijsouw T, Weber J, Broeke J, Broek J, Schut D, Kroon T, et al. Munc18-1 redistributes in nerve terminals in an activity- and PKC-dependent manner. J Cell Biol. 2014;204:759-75 pubmed publisher
    ..Hence, PKC-dependent dynamic control of Munc18-1 levels enables individual synapses to tune their output during periods of activity...
  19. Genç O, Kochubey O, Toonen R, Verhage M, Schneggenburger R. Munc18-1 is a dynamically regulated PKC target during short-term enhancement of transmitter release. elife. 2014;3:e01715 pubmed publisher
    ..Thus, a dynamic PKC phosphorylation/de-phosphorylation cycle of Munc18-1 drives short-term enhancement of transmitter release during PTP. DOI: ..
  20. Parisotto D, Malsam J, Scheutzow A, Krause J, Sollner T. SNAREpin assembly by Munc18-1 requires previous vesicle docking by synaptotagmin 1. J Biol Chem. 2012;287:31041-9 pubmed publisher
    ..Thus, at the neuronal synapse, the priming factor Munc18-1 may accelerate the conversion of docked synaptic vesicles into a readily releasable pool by activating SNAREs for efficient membrane fusion. ..
  21. Park J, Jung M, Kim Y, Song W, Chung S. Phosphorylation of Munc18-1 by Dyrk1A regulates its interaction with Syntaxin 1 and X11?. J Neurochem. 2012;122:1081-91 pubmed publisher
  22. De Marco García N, Priya R, Tuncdemir S, Fishell G, Karayannis T. Sensory inputs control the integration of neurogliaform interneurons into cortical circuits. Nat Neurosci. 2015;18:393-401 pubmed publisher
  23. Cao L, Wang F, Yang Q, Jiang W, Wang C, Chen Y, et al. Reduced thyroid hormones with increased hippocampal SNAP-25 and Munc18-1 might involve cognitive impairment during aging. Behav Brain Res. 2012;229:131-7 pubmed publisher
    ..These results suggested that increased hippocampal SNAP-25 and Munc18-1 which seemingly result from decreased serum THs might involve the age-related impairment of spatial learning and memory. ..
  24. Shen C, Rathore S, Yu H, Gulbranson D, Hua R, Zhang C, et al. The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis. Nat Commun. 2015;6:8852 pubmed publisher
    ..Finally, we show that the trans-SNARE-regulating function of Munc18-1 is compromised by a mutation associated with Ohtahara Syndrome, a severe form of epilepsy. ..
  25. Speidel D, Bruederle C, Enk C, Voets T, Varoqueaux F, Reim K, et al. CAPS1 regulates catecholamine loading of large dense-core vesicles. Neuron. 2005;46:75-88 pubmed
    ..We conclude that CAPS1 is required for an essential step in the uptake or storage of catecholamines in LDCVs. ..
  26. Medrihan L, Rohlmann A, Fairless R, Andrae J, Döring M, Missler M, et al. Neurobeachin, a protein implicated in membrane protein traffic and autism, is required for the formation and functioning of central synapses. J Physiol. 2009;587:5095-106 pubmed publisher
  27. Dallman M, Ladle D. Quantitative analysis of locomotor defects in neonatal mice lacking proprioceptive feedback. Physiol Behav. 2013;120:97-105 pubmed publisher
    ..Step duration and step height are increased in mutant animals. These results underscore the importance of proprioceptive feedback even at early stages in postnatal development. ..
  28. Mandic S, Skelin M, Johansson J, Rupnik M, Berggren P, Bark C. Munc18-1 and Munc18-2 proteins modulate beta-cell Ca2+ sensitivity and kinetics of insulin exocytosis differently. J Biol Chem. 2011;286:28026-40 pubmed publisher
    ..Hence, Munc18-1 and Munc18-2 display distinct subcellular compartmentalization and can coordinate the insulin exocytotic process differently as a consequence of the actual [Ca(2+)](i). ..
  29. Kelkar N, Delmotte M, Weston C, Barrett T, Sheppard B, Flavell R, et al. Morphogenesis of the telencephalic commissure requires scaffold protein JNK-interacting protein 3 (JIP3). Proc Natl Acad Sci U S A. 2003;100:9843-8 pubmed
    ..The central nervous system abnormalities of Jip3-/- mice may be accounted for in part by a reduction in signal transduction by RhoA and its effector ROCK. ..
  30. Bois P, Southgate L, Jeffreys A. Length of uninterrupted repeats determines instability at the unstable mouse expanded simple tandem repeat family MMS10 derived from independent SINE B1 elements. Mamm Genome. 2001;12:104-11 pubmed
    ..The MMS10 family thus provides a potentially useful murine model for studying dynamic mutation at simple tandem repeats. ..
  31. 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
  32. Washbourne P, Thompson P, Carta M, Costa E, Mathews J, Lopez Bendito G, et al. Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis. Nat Neurosci. 2002;5:19-26 pubmed
    ..These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis. ..
  33. 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. ..
  34. Honarpour N, Tabuchi K, Stark J, Hammer R, Sudhof T, Parada L, et al. Embryonic neuronal death due to neurotrophin and neurotransmitter deprivation occurs independent of Apaf-1. Neuroscience. 2001;106:263-74 pubmed
    ..We propose that a switch between apoptotic programs (and their respective proteins) characterizes the transition of a neuronal precursor cell from the progenitor pool to the postmitotic population of differentiated neurons. ..
  35. Schmitz S, King C, Kortleven C, Huson V, Kroon T, Kevenaar J, et al. Presynaptic inhibition upon CB1 or mGlu2/3 receptor activation requires ERK/MAPK phosphorylation of Munc18-1. EMBO J. 2016;35:1236-50 pubmed publisher
    ..Thus, ERK-dependent Munc18-1 phosphorylation provides a major negative feedback loop to control synaptic strength upon activation of presynaptic receptors and during intense neuronal activity. ..
  36. Manent J, Demarque M, Jorquera I, Pellegrino C, Ben Ari Y, Aniksztejn L, et al. A noncanonical release of GABA and glutamate modulates neuronal migration. J Neurosci. 2005;25:4755-65 pubmed
    ..We conclude that GABA and, to a lesser degree, glutamate released in a SNARE-independent mechanism exert a paracrine action on neuronal migration. ..
  37. Fehr C, Shirley R, Crabbe J, Belknap J, Buck K, Phillips T. The syntaxin binding protein 1 gene (Stxbp1) is a candidate for an ethanol preference drinking locus on mouse chromosome 2. Alcohol Clin Exp Res. 2005;29:708-20 pubmed
    ..In the current study, we investigated the association of the syntaxin binding protein 1 gene (Stxbp1) with ethanol preference drinking and other ethanol traits using a panel of B6 x D2 (BXD) ..
  38. Nicol X, Voyatzis S, Muzerelle A, Narboux Nême N, Sudhof T, Miles R, et al. cAMP oscillations and retinal activity are permissive for ephrin signaling during the establishment of the retinotopic map. Nat Neurosci. 2007;10:340-7 pubmed
    ..These results provide a direct molecular link between spontaneous neural activity and axon guidance mechanisms during the refinement of neural maps. ..
  39. Kurps J, de Wit H. The role of Munc18-1 and its orthologs in modulation of cortical F-actin in chromaffin cells. J Mol Neurosci. 2012;48:339-46 pubmed
    ..Our preliminary data suggest that the regulation of cortical F-actin is a shared function of SM proteins, and we propose a way to gain more insight in the molecular mechanism underlying the Munc18-1-mediated cortical F-actin regulation. ..
  40. Wu Z, MacNeil A, Berman J, Lin T. Syntaxin binding protein 1 is not required for allergic inflammation via IgE-mediated mast cell activation. PLoS ONE. 2013;8:e58560 pubmed publisher
    ..However, the function of syntaxin binding protein 1 (STXBP1), a member of SM family, in mast cell degranulation is currently unknown...
  41. Olsen O, Moore K, Fukata M, Kazuta T, Trinidad J, Kauer F, et al. Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex. J Cell Biol. 2005;170:1127-34 pubmed
    ..These findings are consistent with a model whereby the MALS-CASK-liprin-alpha complex recruits components of the synaptic release machinery to adhesive proteins of the active zone. ..
  42. Halachmi N, Lev Z. The Sec1 family: a novel family of proteins involved in synaptic transmission and general secretion. J Neurochem. 1996;66:889-97 pubmed
    ..A working model addressing the dual regulative role of the Sec1 proteins in secretion is presented. ..
  43. Yao I, Takagi H, Ageta H, Kahyo T, Sato S, Hatanaka K, et al. SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release. Cell. 2007;130:943-57 pubmed
    ..Thus, SCRAPPER has an essential function in regulating proteasome-mediated degradation of RIM1 required for synaptic tuning. ..
  44. Dudok J, Groffen A, Toonen R, Verhage M. Deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and early postnatal lethality. PLoS ONE. 2011;6:e28137 pubmed publisher
    ..These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival. ..
  45. 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
  46. Munch A, Kedar G, van Weering J, Vazquez Sanchez S, He E, André T, et al. Extension of Helix 12 in Munc18-1 Induces Vesicle Priming. J Neurosci. 2016;36:6881-91 pubmed publisher
    ..We conclude that a conformational change within helix 12 is responsible for the essential postdocking role of Munc18-1 in neurosecretion. ..
  47. Park S, Bin N, Yu B, Wong R, Sitarska E, Sugita K, et al. UNC-18 and Tomosyn Antagonistically Control Synaptic Vesicle Priming Downstream of UNC-13 in Caenorhabditis elegans. J Neurosci. 2017;37:8797-8815 pubmed publisher
    ..Thus, our study provides novel mechanistic insights into how Munc18/UNC-18 primes synaptic vesicle release and how this protein interacts functionally with Munc13/UNC-13 and Tomosyn/TOM-1. ..
  48. Peng X, Jia Z, Zhang Y, Ware J, Trimble W. The septin CDCrel-1 is dispensable for normal development and neurotransmitter release. Mol Cell Biol. 2002;22:378-87 pubmed
    ..Together, these data suggest that CDCrel-1 is not essential for neuronal development or function, and that changes in expression of other septins may account for its functional redundancy. ..
  49. Hager T, Maroteaux G, Pont P, Julsing J, van Vliet R, Stiedl O. Munc18-1 haploinsufficiency results in enhanced anxiety-like behavior as determined by heart rate responses in mice. Behav Brain Res. 2014;260:44-52 pubmed publisher
    Heterozygous (HZ) missense mutations in the gene encoding syntaxin binding protein 1 (Stxbp1 or Munc18-1), a presynaptic protein essential for neurotransmitter release, causes early infantile epileptic encephalopathy, abnormal brain ..
  50. 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
    ..We conclude that Munc18-1 allows for the formation of a complex between syntaxin and SNAP-25 that serves as an acceptor for vesicle-bound synaptobrevin and that thus represents an intermediate in the pathway towards exocytosis. ..
  51. Lang H, Ai Z, You Z, Wan Y, Guo W, Xiao J, et al. Characterization of miR-218/322-Stxbp1 pathway in the process of insulin secretion. J Mol Endocrinol. 2015;54:65-73 pubmed publisher
    ..b>Stxbp1 plays an essential role in exocytosis, and is crucial for insulin secretion...
  52. Chan A, Khanna R, Li Q, Stanley E. Munc18: a presynaptic transmitter release site N type (CaV2.2) calcium channel interacting protein. Channels (Austin). 2007;1:11-20 pubmed
    ..Thus, the calcium channel may serve as a surface membrane platform anchoring a Munc18-containing bridge to synaptotagmin and the synaptic vesicle. ..
  53. Miyamoto H, Shimohata A, Abe M, Abe T, Mazaki E, Amano K, et al. Potentiation of excitatory synaptic transmission ameliorates aggression in mice with Stxbp1 haploinsufficiency. Hum Mol Genet. 2017;26:4961-4974 pubmed publisher
    ..The STXBP1 gene encodes the syntaxin-binding protein 1 (Munc18-1) that critically controls synaptic vesicle exocytosis and ..