Gene Symbol: STXBP1
Description: syntaxin binding protein 1
Alias: MUNC18-1, NSEC1, P67, RBSEC1, UNC18, syntaxin-binding protein 1, N-Sec1, neuronal SEC1, protein unc-18 homolog 1, protein unc-18 homolog A, unc-18A, unc18-1
Species: human
Products:     STXBP1

Top Publications

  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. Allan B, Moyer B, Balch W. Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion. Science. 2000;289:444-8 pubmed
    ..We propose that Rab1-regulated assembly of functional effector-SNARE complexes defines a conserved molecular mechanism to coordinate recognition between subcellular compartments. ..
  4. Ho C, Marinescu V, Steinhilb M, Gaut J, Turner R, Stuenkel E. Synergistic effects of Munc18a and X11 proteins on amyloid precursor protein metabolism. J Biol Chem. 2002;277:27021-8 pubmed
    ..We conclude that Munc18a acts through direct and indirect interactions with X11 proteins and powerfully regulates APP metabolism and Abeta secretion. ..
  5. Barclay J, Craig T, Fisher R, Ciufo L, Evans G, Morgan A, et al. Phosphorylation of Munc18 by protein kinase C regulates the kinetics of exocytosis. J Biol Chem. 2003;278:10538-45 pubmed
    ..Phosphorylation of Munc18 by PKC may provide a mechanism for the control of exocytosis and thereby synaptic plasticity. ..
  6. Liu J, Ernst S, Gladycheva S, Lee Y, Lentz S, Ho C, et al. Fluorescence resonance energy transfer reports properties of syntaxin1a interaction with Munc18-1 in vivo. J Biol Chem. 2004;279:55924-36 pubmed
    ..We conclude that FRET imaging in living cells may allow correlated regulation of Munc18-1/syntaxin1A interactions to Ca(2+)-regulated secretory events. ..
  7. Rickman C, Medine C, Bergmann A, Duncan R. Functionally and spatially distinct modes of munc18-syntaxin 1 interaction. J Biol Chem. 2007;282:12097-103 pubmed
    ..Furthermore, these functionally divergent interactions occur at distinct cellular locations. These findings provide a molecular explanation for the multiple, spatially distinct roles of munc18-1. ..
  8. Connell E, Darios F, Broersen K, Gatsby N, Peak Chew S, Rickman C, et al. Mechanism of arachidonic acid action on syntaxin-Munc18. EMBO Rep. 2007;8:414-9 pubmed
  9. Jiang B, Lv Q, Wan W, Le L, Xu L, Hu K, et al. Transcriptome analysis reveals the mechanism of the effect of flower tea Coreopsis tinctoria on hepatic insulin resistance. Food Funct. 2018;9:5607-5620 pubmed publisher
    ..g., Rasd1, Stxbp1 and Sfxn1)...

More Information

Publications149 found, 100 shown here

  1. Ou L, Przybilla M, Whitley C. Proteomic analysis of mucopolysaccharidosis I mouse brain with two-dimensional polyacrylamide gel electrophoresis. Mol Genet Metab. 2017;120:101-110 pubmed publisher
    ..Cytoskeletal proteins including ACTA1, ACTN4, TUBB4B and DNM1 were significantly downregulated. STXBP1, a regulator of synaptic vesicle fusion and docking was also downregulated, indicating impaired synaptic ..
  2. Liu J, Tong L, Song S, Niu Y, Li J, Wu X, et al. Novel and de novo mutations in pediatric refractory epilepsy. Mol Brain. 2018;11:48 pubmed publisher
    ..8% (11/16) were novel in Dravet syndrome. Pathogenic or likely pathogenic variants were found in the KCNQ2, STXBP1, SCN2A genes in Ohtahara syndrome...
  3. Popek M, Bobula B, Sowa J, Hess G, Polowy R, Filipkowski R, et al. Cortical Synaptic Transmission and Plasticity in Acute Liver Failure Are Decreased by Presynaptic Events. Mol Neurobiol. 2018;55:1244-1258 pubmed publisher
    ..Our findings demonstrate that a decrease of synaptic transmission in symptomatic ALF is associated with inefficient recruitment of sv proteins and/or impaired sv trafficking to transmitter release sites. ..
  4. Braidy N, Essa M, Poljak A, Selvaraju S, Al Adawi S, Manivasagm T, et al. Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease. Oncotarget. 2016;7:64589-64604 pubmed publisher
    ..Therefore, long-term supplementation with pomegranates can attenuate AD pathology by reducing inflammation, and altering APP-dependent processes. ..
  5. Darlington T, McCarthy R, Cox R, Miyamoto Ditmon J, Gallego X, Ehringer M. Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling. Genes Brain Behav. 2016;15:474-90 pubmed publisher
    ..interaction between ethanol consumption and wheel running include multiple potassium channel genes, Oprm1, Prkcg, Stxbp1, Crhr1, Gabra3, Slc6a13, Stx1b, Pomc, Rassf5 and Camta2...
  6. Dimassi S, Labalme A, Ville D, Calender A, Mignot C, Boutry Kryza N, et al. Whole-exome sequencing improves the diagnosis yield in sporadic infantile spasm syndrome. Clin Genet. 2016;89:198-204 pubmed publisher
    ..MRI), metabolic screening, array-comparative genomic hybridization (CGH) and testing for mutations in CDKL5, STXBP1, and for ARX duplications. We found a probably pathogenic mutation in four patients...
  7. Zhou J, Liu Z, Yu J, Han X, Fan S, Shao W, et al. Quantitative Proteomic Analysis Reveals Molecular Adaptations in the Hippocampal Synaptic Active Zone of Chronic Mild Stress-Unsusceptible Rats. Int J Neuropsychopharmacol. 2015;19: pubmed publisher
  8. Butler K, da Silva C, Alexander J, Hegde M, Escayg A. Diagnostic Yield From 339 Epilepsy Patients Screened on a Clinical Gene Panel. Pediatr Neurol. 2017;77:61-66 pubmed publisher which disease-causing variants were identified in multiple individuals included CDKL5, SCN2A, SCN8A, SCN1B, STXBP1, TPP1, PCDH19, CACNA1A, GABRA1, GRIN2A, SLC2A1, and TSC2...
  9. Da Silva Xavier G, Loder M, McDonald A, Tarasov A, Carzaniga R, Kronenberger K, et al. TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells. Diabetes. 2009;58:894-905 pubmed publisher
    ..TCF7L2 is involved in maintaining expression of beta-cell genes regulating secretory granule fusion. Defective insulin exocytosis may thus underlie increased diabetes incidence in carriers of the at-risk TCF7L2 alleles. ..
  10. Lazarevic V, Yang Y, Ivanova D, Fejtova A, Svenningsson P. Riluzole attenuates the efficacy of glutamatergic transmission by interfering with the size of the readily releasable neurotransmitter pool. Neuropharmacology. 2018;143:38-48 pubmed publisher
    ..This effect was correlated with the inhibition of protein kinase C-dependent Munc18-1 phosphorylation which is known to interfere with neurotransmitter release. ..
  11. Dachtler J, Glasper J, Cohen R, Ivorra J, Swiffen D, Jackson A, et al. Deletion of α-neurexin II results in autism-related behaviors in mice. Transl Psychiatry. 2014;4:e484 pubmed publisher
    ..Quantification of protein expression revealed that Munc18-1, encoded by Stxbp1, was significantly decreased in the hippocampus of Nrxn2α KO mice, which is suggestive of deficiencies in ..
  12. Mastrangelo M. Lennox-Gastaut Syndrome: A State of the Art Review. Neuropediatrics. 2017;48:143-151 pubmed publisher
    ..associated with late-onset cases or pathogenic mutations involving genes, such as GABRB3, ALG13, SCN8A, STXBP1, DNM1, FOXG1, or CHD2...
  13. Vlaskamp D, Rump P, Callenbach P, Vos Y, Sikkema Raddatz B, van Ravenswaaij Arts C, et al. Haploinsufficiency of the STX1B gene is associated with myoclonic astatic epilepsy. Eur J Paediatr Neurol. 2016;20:489-92 pubmed publisher
    ..Furthermore, STX1B encodes for syntaxin-1B, of which interaction with the protein encoded by the STXBP1 gene is essential for the regulation of the synaptic transmission of neurotransmitters...
  14. Sakamoto T, Seiki M. Integrated functions of membrane-type 1 matrix metalloproteinase in regulating cancer malignancy: Beyond a proteinase. Cancer Sci. 2017;108:1095-1100 pubmed publisher
    ..In this review, we summarize recent findings relating to how MT1-MMP activates HIF and its effects on cancer cells and stromal cells. ..
  15. Le S, Le P, Le T, Kieu Huynh T, Hang Do T. A mutation in GABRB3 associated with Dravet syndrome. Am J Med Genet A. 2017;173:2126-2131 pubmed publisher
    ..some simplex patients have variants in one of several other genes, including but not limited to GABRA1, SCN2A, STXBP1, GABRG2, and SCN1B...
  16. Zerem A, Lev D, Blumkin L, Goldberg Stern H, Michaeli Yossef Y, Halevy A, et al. Paternal germline mosaicism of a SCN2A mutation results in Ohtahara syndrome in half siblings. Eur J Paediatr Neurol. 2014;18:567-71 pubmed publisher
    ..such as Dravet syndrome, KCNQ2 neonatal epileptic encephalopathy, SCN8A epileptic encephalopathy and STXBP1 related Ohtahara syndrome...
  17. Wang C, Zhao D, Shah S, Yang W, Li C, Yang L. Proteome Analysis of Potential Synaptic Vesicle Cycle Biomarkers in the Cerebrospinal Fluid of Patients with Sporadic Creutzfeldt-Jakob Disease. Mol Neurobiol. 2017;54:5177-5191 pubmed publisher
    ..Six key proteins, such as AP2A1, SYT1, SNAP25, STXBP1, CLTB, and Rab3a, showed the same trend by western blot as detected by iTRAQ...
  18. Gürsoy S, Erçal D. Diagnostic Approach to Genetic Causes of Early-Onset Epileptic Encephalopathy. J Child Neurol. 2016;31:523-32 pubmed publisher
    ..To date, approximately 265 genes have been defined in epilepsy and several genes including STXBP1, ARX, SLC25A22, KCNQ2, CDKL5, SCN1A, and PCDH19 have been found to be associated with early-onset epileptic ..
  19. Baguma Nibasheka M, Fracassi A, Costain W, Moreno S, Kablar B. Role of skeletal muscle in motor neuron development. Histol Histopathol. 2016;31:699-719 pubmed publisher
    ..Several follow-up steps revealed that Kif5c, Stxbp1 and Polb, differentially expressed in the MyoD-/- limb muscle, and Ppargc1a, Glrb and Hoxd10, differentially ..
  20. Hewson S, Brunga L, Ojeda M, Imhof E, Patel J, Zak M, et al. Prevalence of Genetic Disorders and GLUT1 Deficiency in a Ketogenic Diet Clinic. Can J Neurol Sci. 2017;:1-4 pubmed publisher
    ..ceroid lipofuscinosis type II, mitochondrial disorders, tuberous sclerosis, lissencephaly, and SCN1A-, SCN8A-, and STXBP1-associated epileptic encephalopathies...
  21. Triplett J, Swomley A, Kirk J, Grimes K, Lewis K, Orr M, et al. Reaching Out to Send a Message: Proteins Associated with Neurite Outgrowth and Neurotransmission are Altered with Age in the Long-Lived Naked Mole-Rat. Neurochem Res. 2016;41:1625-34 pubmed publisher
    ..We hypothesize that such changes may contribute to the extended lifespan and healthspan of the NMR. ..
  22. Ortega Moreno L, Giráldez B, Soto Insuga V, Losada Del Pozo R, Rodrigo Moreno M, Alarcón Morcillo C, et al. Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes. PLoS ONE. 2017;12:e0188978 pubmed publisher
    ..5%) analyzed patients, all found in known epilepsy-associated genes (KCNQ2, CDKL5, STXBP1, SCN1A, PCDH19, POLG, SLC2A1, ARX, ALG13, CHD2, SYNGAP1, and GRIN1)...
  23. Schönewolf Greulich B, Bisgaard A, Møller R, Dunø M, Brøndum Nielsen K, Kaur S, et al. Clinician's guide to genes associated with Rett-like phenotypes - Investigation of a Danish cohort and review of the literature. Clin Genet. 2017;: pubmed publisher
    ..syndrome, Cornelia de Lange syndrome with SMC1A variants, and epileptic encephalopathies for example due to STXBP1 variants...
  24. Kato M. [Topics of brain malformation and epilepsy--age-dependent epileptic encephalopathies and interneuronopathies]. No To Hattatsu. 2010;42:333-8 pubmed
    ..We identified the second gene responsible for Ohtahara syndrome, STXBP1, which is essential for synaptic vesicle release...
  25. Wang W, Jia Y, Pham D, Palmer L, Jung K, Cox C, et al. Atypical Endocannabinoid Signaling Initiates a New Form of Memory-Related Plasticity at a Cortical Input to Hippocampus. Cereb Cortex. 2018;28:2253-2266 pubmed publisher
    ..These results link atypical ECB signaling to the encoding of a fundamental component of episodic memory and suggest a novel route whereby endogenous and exogenous cannabinoids affect cognition. ..
  26. Cornet M, SANDS T, Cilio M. Neonatal epilepsies: Clinical management. Semin Fetal Neonatal Med. 2018;23:204-212 pubmed publisher
    ..g., channelopathies, STXBP1)...
  27. Sleat D, Tannous A, Sohar I, Wiseman J, Zheng H, Qian M, et al. Proteomic Analysis of Brain and Cerebrospinal Fluid from the Three Major Forms of Neuronal Ceroid Lipofuscinosis Reveals Potential Biomarkers. J Proteome Res. 2017;16:3787-3804 pubmed publisher
    ..Significant alterations in protein expression were identified in each NCL, including reduced STXBP1 in CLN1 disease brain...
  28. Valence S, Cochet E, Rougeot C, Garel C, Chantot Bastaraud S, Lainey E, et al. Exome sequencing in congenital ataxia identifies two new candidate genes and highlights a pathophysiological link between some congenital ataxias and early infantile epileptic encephalopathies. Genet Med. 2019;21:553-563 pubmed publisher illustrates the diversity of the pathophysiological pathways in CA, and highlights the pathogenic link between some CA and early infantile epileptic encephalopathies related to the same genes (STXBP1, BRAT1, CACNA1A and CACNA2D2).
  29. Zhang X, Rebane A, Ma L, Li F, Jiao J, Qu H, et al. Stability, folding dynamics, and long-range conformational transition of the synaptic t-SNARE complex. Proc Natl Acad Sci U S A. 2016;113:E8031-E8040 pubmed
    ..Thus, the t-SNARE complex acted as a switch to enable fast and controlled SNARE zippering required for synaptic vesicle fusion and neurotransmission. ..
  30. Hackmann Y, Graham S, Ehl S, Höning S, Lehmberg K, Aricò M, et al. Syntaxin binding mechanism and disease-causing mutations in Munc18-2. Proc Natl Acad Sci U S A. 2013;110:E4482-91 pubmed publisher
    ..Similarly, Munc18-1, expressed in IL-2-activated CTL, is capable of binding Stx11. These findings provide potential explanations for restoration of Munc18-Stx function and cytotoxicity in IL-2-activated cells. ..
  31. Huai W, Song H, Yu Z, Wang W, Han L, Sakamoto T, et al. Mint3 potentiates TLR3/4- and RIG-I-induced IFN-? expression and antiviral immune responses. Proc Natl Acad Sci U S A. 2016;113:11925-11930 pubmed
    ..Therefore, we have identified Mint3 as a physiological positive regulator of TLR3/4 and RIG-I-induced IFN-? production and have outlined a feedback mechanism for the control of antiviral immune responses. ..
  32. Wang T, Guo H, Xiong B, Stessman H, Wu H, Coe B, et al. De novo genic mutations among a Chinese autism spectrum disorder cohort. Nat Commun. 2016;7:13316 pubmed publisher
    ..GIGYF2, MYT1L, CUL3, DOCK8 and ZNF292) and DN mutations in previous ASD candidates (ARHGAP32, NCOR1, PHIP, STXBP1, CDKL5 and SHANK1)...
  33. Milh M, Cacciagli P, Ravix C, Badens C, Lepine A, Villeneuve N, et al. Severe neonatal seizures: From molecular diagnosis to precision therapy?. Rev Neurol (Paris). 2016;172:171-3 pubmed publisher
    ..In this short review, we show that two mains genes are involved in EOEE: STXBP1 and KCNQ2...
  34. Mizuno K, Fujita T, Gomi H, Izumi T. Granuphilin exclusively mediates functional granule docking to the plasma membrane. Sci Rep. 2016;6:23909 pubmed publisher
    ..These findings indicate that granuphilin is an exclusive component of the functional and fusion-inhibitory docking machinery of secretory granules. ..
  35. Shimojima K, Okamoto N, Goel H, Ondo Y, Yamamoto T. Familial 9q33q34 microduplication in siblings with developmental disorders and macrocephaly. Eur J Med Genet. 2017;60:650-654 pubmed publisher
    ..Their mother was a mosaic carrier of this duplication. Duplicated regions involved STXBP1; the gene related to epileptic encephalopathy...
  36. 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
  37. Carvill G, Weckhuysen S, McMahon J, Hartmann C, Møller R, Hjalgrim H, et al. GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology. 2014;82:1245-53 pubmed publisher
    ..detected disease-causing mutations in 2 novel genes for Dravet syndrome, with mutations in GABRA1 in 4 cases and STXBP1 in 3...
  38. Yang X, Wang S, Sheng Y, Zhang M, Zou W, Wu L, et al. Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming. Nat Struct Mol Biol. 2015;22:547-54 pubmed publisher
    ..These results support the notion that orchestration of syntaxin-1 opening and SNARE-complex assembly underlies the central role of UNC-13-Munc13s in synaptic-vesicle priming. ..
  39. 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...
  40. Toft Bertelsen T, Ziomkiewicz I, Houy S, Pinheiro P, Sørensen J. Regulation of Ca2+ channels by SNAP-25 via recruitment of syntaxin-1 from plasma membrane clusters. Mol Biol Cell. 2016;27:3329-3341 pubmed
    ..This mechanism potentially allows the cell to regulate Ca2+ influx by expanding or contracting syntaxin-1 clusters. ..
  41. Gutierrez B, Chavez M, Rodarte A, Ramos M, Dominguez A, Petrova Y, et al. Munc18-2, but not Munc18-1 or Munc18-3, controls compound and single-vesicle-regulated exocytosis in mast cells. J Biol Chem. 2018;293:7148-7159 pubmed publisher
    ..In conclusion, MC-regulated exocytosis is required for the anaphylactic response, and Munc18-2 is the sole Munc18 isoform that mediates membrane fusion during MC degranulation. ..
  42. Reed G, Houng A, Fitzgerald M. Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion. Blood. 1999;93:2617-26 pubmed
  43. Quick M. The role of SNARE proteins in trafficking and function of neurotransmitter transporters. Handb Exp Pharmacol. 2006;:181-96 pubmed
    ..In this chapter, the functional effects of syntaxin-transporter interactions are reviewed, and how such interactions may regulate neuronal signaling are considered. ..
  44. Saxena S, Singh M, Kaur S, George C. Distinct domain-dependent effect of syntaxin1A on amiloride-sensitive sodium channel (ENaC) currents in HT-29 colonic epithelial cells. Int J Biol Sci. 2006;3:47-56 pubmed
    ..We propose that syntaxin1A possesses distinct inhibitory and stimulatory domains that interact with ENaC subunits, which critically determines the overall ENaC functionality/regulation under distinct physiological conditions. ..
  45. Kasula R, Chai Y, Bademosi A, Harper C, Gormal R, Morrow I, et al. The Munc18-1 domain 3a hinge-loop controls syntaxin-1A nanodomain assembly and engagement with the SNARE complex during secretory vesicle priming. J Cell Biol. 2016;214:847-58 pubmed publisher
    ..Accordingly, syntaxin-1A confinement was prevented by expression of botulinum neurotoxin type E. The Munc18-1 domain 3a hinge-loop therefore controls syntaxin-1A engagement into SNARE complex formation during priming. ..
  46. Meijer M, Cijsouw T, Toonen R, Verhage M. Synaptic Effects of Munc18-1 Alternative Splicing in Excitatory Hippocampal Neurons. PLoS ONE. 2015;10:e0138950 pubmed publisher
    ..Our data suggest that alternative splicing of Munc18-1 support synaptic transmission to a similar extent, but could modulate presynaptic short-term plasticity. ..
  47. Gil Pisa I, Munarriz Cuezva E, Ramos Miguel A, Urigüen L, Meana J, Garcia Sevilla J. Regulation of munc18-1 and syntaxin-1A interactive partners in schizophrenia prefrontal cortex: down-regulation of munc18-1a isoform and 75 kDa SNARE complex after antipsychotic treatment. Int J Neuropsychopharmacol. 2012;15:573-88 pubmed publisher
    ..Moreover, antipsychotic drug treatment is associated with lower content of key proteins of the exocytotic machinery, which could result in a destabilization/impairment of neurosecretion. ..
  48. 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. ..
  49. Saitsu H, Kato M, Okada I, Orii K, Higuchi T, Hoshino H, et al. STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern. Epilepsia. 2010;51:2397-405 pubmed publisher
    De novo STXBP1 mutations have been found in individuals with early infantile epileptic encephalopathy with suppression-burst pattern (EIEE)...
  50. Vardar G, Chang S, Arancillo M, Wu Y, Trimbuch T, Rosenmund C. Distinct Functions of Syntaxin-1 in Neuronal Maintenance, Synaptic Vesicle Docking, and Fusion in Mouse Neurons. J Neurosci. 2016;36:7911-24 pubmed publisher
    ..Therefore, our work provides insights into differential functions of Stx1 in neuronal maintenance and neurotransmission, with the latter explored further into its functions in vesicle docking and fusion. ..
  51. Deshpande M, Rodal A. Beyond the SNARE: Munc18-1 chaperones α-synuclein. J Cell Biol. 2016;214:641-3 pubmed publisher
    ..In this issue, Chai et al. (2016. J. Cell Biol find that Munc18-1 is a molecular chaperone for α-synuclein and that aggregated Munc18-1 EIEE-causing mutants promote α-synuclein aggregation. ..
  52. Sitarska E, Xu J, Park S, Liu X, Quade B, Stepien K, et al. Autoinhibition of Munc18-1 modulates synaptobrevin binding and helps to enable Munc13-dependent regulation of membrane fusion. elife. 2017;6: pubmed publisher
  53. 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. ..
  54. Liu X, Hao W, Qin Y, Decker Y, Wang X, Burkart M, et al. Long-term treatment with Ginkgo biloba extract EGb 761 improves symptoms and pathology in a transgenic mouse model of Alzheimer's disease. Brain Behav Immun. 2015;46:121-31 pubmed publisher
    ..Therefore, long-term treatment with G. biloba extract EGb 761, a clinically available and well-tolerated herbal medication, ameliorates AD pathology by antiinflammatory and Aβ-directed mechanisms. ..
  55. Gburek Augustat J, Beck Woedl S, Tzschach A, Bauer P, Schoening M, Riess A. Epilepsy is not a mandatory feature of STXBP1 associated ataxia-tremor-retardation syndrome. Eur J Paediatr Neurol. 2016;20:661-5 pubmed publisher
    Mutations in the STXBP1 gene (MUNC18-1) were first described to cause Ohtahara syndrome (Early infantile epileptic encephalopathy, EIEE)(12-14) characterized by very early infantile epileptic encephalopathy with frequent tonic spasms and ..
  56. Gokben S, Onay H, Yilmaz S, AtIk T, Serdaroglu G, Tekin H, et al. Targeted next generation sequencing: the diagnostic value in early-onset epileptic encephalopathy. Acta Neurol Belg. 2017;117:131-138 pubmed publisher
    ..sixteen genes (ARX, CDKL5, CNTNAP2, FOLR1, FOXG1, LAMC3, MBD5, MECP2, NTNG1, PCDH19, PNKP, SCN1A, SCN1B, SCN2A, STXBP1, KCNQ2) was constituted. Nine definite and three potential causal mutations in 30 cases (40 %) were identified...
  57. Edwards M, Johnson J, Rankin K, Jenkins R, Maguire C, Morgan A, et al. PKC-2 phosphorylation of UNC-18 Ser322 in AFD neurons regulates temperature dependency of locomotion. J Neurosci. 2012;32:7042-51 pubmed publisher
    ..These data demonstrate that an individual DAG-dependent thermosensory behavior of an organism is effected specifically by the downstream PKC-2 phosphorylation of UNC-18 on Ser322 in AFD neurons. ..
  58. 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
    ..Although the Sec1/Munc18 family may serve as part of the fusion machinery in other exocytotic pathways, Munc18-1 may have evolved to play a different role, such as regulating syntaxin-1a in neuroexocytosis. ..
  59. Meng J, Wang J, Steinhoff M, Dolly J. TNFα induces co-trafficking of TRPV1/TRPA1 in VAMP1-containing vesicles to the plasmalemma via Munc18-1/syntaxin1/SNAP-25 mediated fusion. Sci Rep. 2016;6:21226 pubmed publisher
  60. Liu D, Xu X, Zhuang M, Song M, Qin W, Wang X, et al. [Suppressive effect of exogenous carbon monoxide on abnormal platelet exocytosis and its molecular mechanism in sepsis]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016;28:110-6 pubmed publisher
    ..The expressions of Toll-like receptor 4 (TLR4), phosphorylation of protein kinase Cθ (PKCθ) and syntaxin binding protein 1 (STXBP-1) were determined by Western Bolt...
  61. Jakhanwal S, Lee C, Urlaub H, Jahn R. An activated Q-SNARE/SM protein complex as a possible intermediate in SNARE assembly. EMBO J. 2017;36:1788-1802 pubmed publisher
    ..Moreover, the complex is resistant to disassembly by NSF Based on these findings, we consider the ternary complex as a strong candidate for a physiological intermediate in SNARE assembly. ..
  62. Schillemans M, Karampini E, van den Eshof B, Gangaev A, Hofman M, van Breevoort D, et al. Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells. Arterioscler Thromb Vasc Biol. 2018;38:1549-1561 pubmed publisher
    ..We have previously identified STXBP1 as the link between the Rab27A-Slp4-a complex on WPBs and the SNARE proteins syntaxin-2 and -3...
  63. 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
    b>rbSec1 is a mammalian neuronal protein homologous to the yeast SEC1 gene product which is required for exocytosis. Mutations in Sec1 homologues in the nervous systems of C. elegans and D...
  64. 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
  65. 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. ..
  66. Orock A, Logan S, Deak F. Munc18-1 haploinsufficiency impairs learning and memory by reduced synaptic vesicular release in a model of Ohtahara syndrome. Mol Cell Neurosci. 2018;88:33-42 pubmed publisher
    ..EIEE-4 patients have mutations most frequently in the STXBP1 gene encoding a Sec protein, munc18-1...
  67. Rizo J, Xu J. The Synaptic Vesicle Release Machinery. Annu Rev Biophys. 2015;44:339-67 pubmed publisher
    ..Although alternative models exist and fundamental questions remain unanswered, a definitive description of the basic release mechanism may be available soon. ..
  68. Helbig K, Farwell Hagman K, Shinde D, Mroske C, Powis Z, Li S, et al. Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. Genet Med. 2016;18:898-905 pubmed publisher
    ..4% (105/314). KCNQ2, MECP2, FOXG1, IQSEC2, KMT2A, and STXBP1 were most commonly affected by de novo alterations...
  69. 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 ..
  70. Hamada N, Iwamoto I, Tabata H, Nagata K. MUNC18-1 gene abnormalities are involved in neurodevelopmental disorders through defective cortical architecture during brain development. Acta Neuropathol Commun. 2017;5:92 pubmed publisher
    ..Disruption of Munc18-1 function may result in the abnormal corticogenesis, leading to neurodevelopmental disorders with MUNC18-1 gene abnormalities. ..
  71. Murphy S, Zweyer M, Henry M, Meleady P, Mundegar R, Swandulla D, et al. Label-free mass spectrometric analysis reveals complex changes in the brain proteome from the mdx-4cv mouse model of Duchenne muscular dystrophy. Clin Proteomics. 2015;12:27 pubmed publisher
    ..Candidate proteins can now be evaluated for their suitability as proteomic biomarkers and their potential in predictive, diagnostic, prognostic and/or therapy-monitoring approaches to treat brain abnormalities in dystrophinopathies. ..
  72. 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. ..
  73. 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. ..
  74. Santos T, Wierda K, Broeke J, Toonen R, Verhage M. Early Golgi Abnormalities and Neurodegeneration upon Loss of Presynaptic Proteins Munc18-1, Syntaxin-1, or SNAP-25. J Neurosci. 2017;37:4525-4539 pubmed publisher
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    ..These results implicate that the two SNAP-25 isoforms could differently mediate protein interactions outside the ternary SNARE core complex and thereby contribute to modulate neurotransmission. ..
  76. Di Meglio C, Lesca G, Villeneuve N, Lacoste C, Abidi A, Cacciagli P, et al. Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases. Epilepsia. 2015;56:1931-40 pubmed publisher
    Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome, with a mutation detection rate of approximately 10%, depending on the ..
  77. Ko A, Youn S, Kim S, Lee J, Kim S, Choi J, et al. Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy. Epilepsy Res. 2018;141:48-55 pubmed publisher
    ..the highest among patients with West syndrome (WS) with a history of neonatal seizures and mutations in KCNQ2 and STXBP1 were most frequently identified...
  78. Colbert K, Hattendorf D, Weiss T, Burkhardt P, Fasshauer D, Weis W. Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to Munc18a in a closed conformation. Proc Natl Acad Sci U S A. 2013;110:12637-42 pubmed publisher
    ..Although the role of the N-peptide in Munc18a-mediated SNARE complex assembly remains unclear, our results demonstrate that the N-peptide and LE mutation have no effect on the global conformation of the Munc18a-Syx1a complex. ..
  79. Datta P, Allamargot C, Hudson J, Andersen E, Bhattarai S, Drack A, et al. Accumulation of non-outer segment proteins in the outer segment underlies photoreceptor degeneration in Bardet-Biedl syndrome. Proc Natl Acad Sci U S A. 2015;112:E4400-9 pubmed publisher
    ..We found striking accumulation of Stx3 and Stxbp1/Munc18-1 and loss of polarized localization of Prom1 within the Lztfl1 and Bbs1 mutant OS...
  80. Patzke C, Han Y, Covy J, Yi F, Maxeiner S, Wernig M, et al. Analysis of conditional heterozygous STXBP1 mutations in human neurons. J Clin Invest. 2015;125:3560-71 pubmed publisher
    Heterozygous mutations in the syntaxin-binding protein 1 (STXBP1) gene, which encodes Munc18-1, a core component of the presynaptic membrane-fusion machinery, cause infantile early epileptic encephalopathy (Ohtahara syndrome), but it is ..
  81. Marchese M, Valvo G, Moro F, Sicca F, Santorelli F. Targeted Gene Resequencing (Astrochip) to Explore the Tripartite Synapse in Autism-Epilepsy Phenotype with Macrocephaly. Neuromolecular Med. 2016;18:69-80 pubmed publisher
    ..or previously unknown predicted deleterious missense changes in GJA1, SLC12A2, SNTA1, EFNA3, CNTNAP2, EPHA4, and STXBP1 in seven patients and two high-frequency variants in DLG1 in six individuals...
  82. Ma L, Rebane A, Yang G, Xi Z, Kang Y, Gao Y, et al. Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis. elife. 2015;4: pubmed publisher
    ..Our observations demonstrate distinct functions of SNARE domains whose assembly is intimately chaperoned by Munc18-1. ..
  83. Sidhu V, Huang B, Desai A, Kevala K, Kim H. Role of DHA in aging-related changes in mouse brain synaptic plasma membrane proteome. Neurobiol Aging. 2016;41:73-85 pubmed publisher
    ..Our results suggest a potential role of DHA in alleviating aging-associated cognitive decline by offsetting the loss of neurotransmission-regulating synaptic proteins involved in synaptic function. ..
  84. 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
    ..These studies demonstrate a clear role for SM proteins in platelet exocytosis and aggregation and suggest a dominant role for Munc18c in all three granule-release events...
  85. Stamberger H, Nikanorova M, Willemsen M, Accorsi P, Angriman M, Baier H, et al. STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. Neurology. 2016;86:954-62 pubmed publisher
    To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients...
  86. Graham M, Prescott G, Johnson J, Jones M, Walmesley A, Haynes L, et al. Structure-function study of mammalian Munc18-1 and C. elegans UNC-18 implicates domain 3b in the regulation of exocytosis. PLoS ONE. 2011;6:e17999 pubmed publisher
    ..elegans). These data implicate a novel role for an exposed loop in domain 3b of Munc18-1 in transducing regulation of vesicle fusion independent of closed-conformation syntaxin binding. ..
  87. Salunkhe V, Ofori J, Gandasi N, Salö S, Hansson S, Andersson M, et al. MiR-335 overexpression impairs insulin secretion through defective priming of insulin vesicles. Physiol Rep. 2017;5: pubmed publisher
    ..and OE335 cells showed concomitant reduction in three exocytotic proteins: SNAP25, Syntaxin-binding protein 1 (STXBP1), and synaptotagmin 11 (SYT11)...
  88. Lopez J, Noori T, Minson A, Li Jovanoska L, Thia K, Hildebrand M, et al. Bi-Allelic Mutations in STXBP2 Reveal a Complementary Role for STXBP1 in Cytotoxic Lymphocyte Killing. Front Immunol. 2018;9:529 pubmed publisher
    ..STXBP2 and STX11 proteins, we also observed a concomitant significant reduction in the expression of homologous STXBP1 protein and its partner STX1, which had never been implicated in CL function...
  89. Han G, Malintan N, Collins B, Meunier F, Sugita S. Munc18-1 as a key regulator of neurosecretion. J Neurochem. 2010;115:1-10 pubmed publisher
    ..In this review, we summarize these recent advances and attempt to propose an updated model of the pleiotropic functions of Munc18-1 in neuroexocytosis. ..
  90. Verhage M, de Vries K, Røshol H, Burbach J, Gispen W, Sudhof T. DOC2 proteins in rat brain: complementary distribution and proposed function as vesicular adapter proteins in early stages of secretion. Neuron. 1997;18:453-61 pubmed
    ..These data suggest that DOC2 proteins are vesicular adapter proteins regulating munc18-syntaxin complexes and herewith synaptic vesicle docking. ..
  91. 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. ..
  92. Swanson D, Steel J, Valle D. Identification and characterization of the human ortholog of rat STXBP1, a protein implicated in vesicle trafficking and neurotransmitter release. Genomics. 1998;48:373-6 pubmed identify genes expressed preferentially in retina, we identified a cDNA encoding the human ortholog of rat STXBP1 (n-Sec1, Munc-18-1, rbSec1), a protein implicated in vesicle trafficking and neurotransmitter release...