Affinage

STXBP1

Syntaxin-binding protein 1 · UniProt P61764

Length
594 aa
Mass
67.6 kDa
Annotated
2026-04-28
100 papers in source corpus 43 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STXBP1 (Munc18-1) is a neuron-enriched Sec1/Munc18-family protein that orchestrates every major step of SNARE-dependent synaptic vesicle exocytosis—from syntaxin-1 chaperoning and trafficking, through vesicle docking and priming, to membrane fusion and fusion-pore regulation. It binds the closed conformation of syntaxin-1 via its central cavity to chaperone syntaxin-1 from the ER to the plasma membrane, then undergoes a conformational transition in its domain 3a hinge-loop/helix 12 that templates SNARE complex assembly cooperatively with Munc13-1, directly engaging synaptobrevin/VAMP2 at the C-terminus of its SNARE motif and promoting sequential trans-SNARE zippering to drive fusion (PMID:8108429, PMID:18596236, PMID:28477408, PMID:31888993, PMID:27358447). Its activity is dynamically regulated by PKC phosphorylation at Ser306/Ser313 (disrupting syntaxin binding and controlling synaptic reclustering), Src-family kinase phosphorylation at Y473 (blocking SNARE templating), S-nitrosylation of syntaxin-1 Cys145, and Ca²⁺-calmodulin–dependent release from presynaptic mGluR4 (PMID:8631738, PMID:24590174, PMID:29150433, PMID:18452404, PMID:19822743). Heterozygous loss-of-function mutations in STXBP1 cause protein destabilization and haploinsufficiency that preferentially impairs inhibitory synaptic transmission, leading to epileptic encephalopathy (including Ohtahara syndrome), while rare mutations such as L446F produce gain-of-function effects on release probability (PMID:29538625, PMID:32073399, PMID:31855252, PMID:26572858).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Identification of STXBP1 as a neural syntaxin-binding protein established that a Sec1-family member directly and specifically engages the t-SNARE syntaxin (but not SNAP-25 or VAMP) at synapses, providing the first molecular handle on SM-protein function in neurotransmitter release.

    Evidence Pulldown assays with syntaxin fusion proteins and brain extracts in two independent laboratories

    PMID:8108429 PMID:8134339

    Open questions at the time
    • No information on whether the interaction was direct or via a complex
    • Binding mode (closed vs. open syntaxin) unknown
    • Functional consequence for exocytosis not yet tested
  2. 1996 High

    Demonstration that PKC phosphorylates Munc18-1 at Ser306/Ser313 and that phosphorylation disrupts syntaxin binding revealed the first regulatory switch controlling the Munc18-1/syntaxin interaction, later confirmed in native nerve terminals and chromaffin cells.

    Evidence In vitro kinase assay with site mapping; subsequently validated in synaptosomes and chromaffin cells with phospho-specific antibodies and depolarization paradigms

    PMID:10651895 PMID:12950453 PMID:8631738

    Open questions at the time
    • In vivo phosphorylation stoichiometry at individual sites not quantified
    • Downstream effect on vesicle pool sizes not directly measured
  3. 1999 High

    Showing that Munc18-1 prevents syntaxin-1A–induced Golgi disruption and is required for syntaxin trafficking to the plasma membrane established a chaperone function distinct from a direct role in fusion, later confirmed in C. elegans neurons.

    Evidence Syntaxin-1A overexpression ± rbSec1 in non-neurosecretory cells; C. elegans unc-18 mutant ER-retention assays

    PMID:10341206 PMID:18596236

    Open questions at the time
    • Whether chaperoning requires a specific closed-conformation lock or simply stoichiometric binding was initially unclear
    • Chaperone function not reconstituted with purified components
  4. 2004 High

    FRET imaging in living cells demonstrated that Munc18-1 and syntaxin-1A first interact at the Golgi and then at the plasma membrane, and that PKC (Ser313) and Cdk5 (Thr574) phosphomimetic mutations reduce the interaction, linking phospho-regulation to the trafficking and exocytic pathways in real time.

    Evidence FRET/FLIM between CFP-Munc18-1 and YFP-syntaxin-1A in HEK293 and chromaffin cells with phosphomimetic mutants

    PMID:15489225

    Open questions at the time
    • Cdk5-mediated phosphorylation at Thr574 not validated with phospho-specific antibodies in neurons
    • Whether Golgi interaction is required for subsequent plasma membrane function not resolved
  5. 2007 High

    Discovery that Munc18-1 binds syntaxin in two modes—closed-conformation binding (promoting docking) and SNARE-complex binding via the syntaxin N-terminus (promoting priming/fusion)—and that disrupting the N-terminal interaction blocks neurotransmitter release at the calyx of Held, established a dual-mode framework for SM-protein function.

    Evidence Co-IP with truncated syntaxins; electrophysiology with competing N-terminal peptide at calyx of Held; Munc18-1 variant rescue in null chromaffin cells with EM and capacitance

    PMID:17687045 PMID:17989281

    Open questions at the time
    • Structural basis for how the two binding modes interconvert was not resolved
    • Whether additional interaction surfaces beyond the N-peptide contribute was unknown
  6. 2010 High

    Biophysical and reconstitution studies showed Munc18-1 directly binds synaptobrevin/VAMP2 and stimulates SNARE-mediated membrane fusion through its central cavity, even without the syntaxin Habc domain, positioning Munc18-1 as a direct fusion catalyst rather than merely a syntaxin clamp.

    Evidence NMR, ITC, and analytical ultracentrifugation for VAMP2 binding; reconstituted liposome fusion with domain-deletion mutants; single-vesicle FRET and EPR

    PMID:20102228 PMID:20300453 PMID:20603329

    Open questions at the time
    • Affinity for VAMP2 was low-micromolar—relevance at synaptic concentrations debated
    • How Munc18-1 coordinates simultaneous binding to syntaxin and synaptobrevin structurally unresolved
  7. 2011 High

    Reconstitution showed Munc18-1 acts as a stage-specific off/on switch: it inhibits fusion when bound to closed syntaxin, then stimulates fusion specifically upon VAMP2 and SNAP-25 addition, while also modulating fusion pore geometry through distinct interaction surfaces.

    Evidence Sequential t-SNARE/v-SNARE liposome fusion assay; patch-clamp capacitance and STED microscopy with Munc18-1 mutants in lactotrophs

    PMID:21677188 PMID:21730064 PMID:21900493

    Open questions at the time
    • How the inhibitory-to-stimulatory transition is triggered at native synapses was not clear
    • Whether fusion pore effects are direct or secondary to SNARE zippering kinetics not resolved
  8. 2013 High

    Domain 3a of Munc18-1—specifically its hinge-loop (residues 317–333) and helix 12—was identified as essential for vesicle priming and SNARE complex binding but dispensable for syntaxin chaperoning, cleanly separating the two major functions of the protein.

    Evidence Domain 3a insertion and deletion mutants rescuing Munc18-1 null/knockdown PC12 cells; exocytosis, EM docking, and SNARE binding assays; EPR of syntaxin conformational exchange

    PMID:23525015 PMID:23561535 PMID:23761923

    Open questions at the time
    • Atomic-resolution structure of the extended helix 12 conformation not yet available
    • Whether domain 3a conformational change is triggered by a specific signal (e.g., Munc13) was unknown
  9. 2015 High

    Heterozygous STXBP1 mutations reduce Munc18-1 and syntaxin-1 protein levels by ~30% each and decrease neurotransmitter release by ~50% in isogenic human neurons, establishing haploinsufficiency as the primary cellular disease mechanism for STXBP1 encephalopathy.

    Evidence Isogenic heterozygous/homozygous human ES cell-derived neurons; electrophysiology and immunoblot

    PMID:26280581

    Open questions at the time
    • Which neuron subtypes are most vulnerable to haploinsufficiency was not determined in the human model
    • Whether protein aggregation contributes to haploinsufficiency in patient neurons was not tested
  10. 2017 High

    Structural and functional work revealed that Munc18-1 templates SNARE complex assembly via an autoinhibited domain 3a loop that, when unfurled (e.g., D326K), specifically binds synaptobrevin and can bypass the Munc13 requirement; Src kinase phosphorylation at Y473 blocks this templating without affecting docking, establishing two orthogonal regulatory inputs on the same priming step.

    Evidence NMR of specific vs. non-specific VAMP2 binding; reconstituted fusion ± Munc13; C. elegans rescue; phosphomimetic Y473D in null hippocampal neurons with electrophysiology

    PMID:28477408 PMID:28821673 PMID:29150433

    Open questions at the time
    • How Munc13 physically unfurls the domain 3a loop was not structurally resolved
    • Whether Y473 phosphorylation occurs under physiological stimulation patterns in vivo not shown
  11. 2018 High

    Multiple disease-associated Munc18-1 mutations were shown to cause protein aggregation that co-aggregates wild-type protein (dominant-negative at the protein level though functionally haploinsufficient), and GABAergic neuron-specific Stxbp1 haploinsufficiency was demonstrated to cause cortical hyperexcitability, pinpointing inhibitory neurons as the vulnerable population.

    Evidence Aggregation assays in yeast, C. elegans, and mouse neurons with chemical chaperone rescue; conditional GABAergic Stxbp1 knockout with EEG and c-Fos

    PMID:29538625 PMID:30266908

    Open questions at the time
    • Whether chemical chaperones are effective in patient-derived neurons not tested
    • Relative contributions of parvalbumin vs. somatostatin interneurons not dissected in these studies
  12. 2019 High

    Single-molecule force spectroscopy quantified Munc13-1 MUN domain stabilization of the Munc18-1/syntaxin-1/VAMP2 template complex by ~2.1 kBT, showing how Munc13 cooperatively promotes full SNARE assembly through this intermediate.

    Evidence Single-molecule force spectroscopy; mutagenesis of MUN-template interface; SNARE assembly and neurotransmitter release assays

    PMID:31888993

    Open questions at the time
    • Whether additional factors (e.g., synaptotagmin, complexin) modulate template stability not measured
    • In vivo relevance of the ~2.1 kBT stabilization energy not confirmed
  13. 2020 High

    A homozygous L446F mutation demonstrated gain-of-function (2-fold increased release probability), showing that not all STXBP1 mutations cause loss of function and that the clinical spectrum includes divergent cellular mechanisms; independently, humanized C. elegans confirmed that most epilepsy-associated variants cause protein instability rather than transcriptional defects.

    Evidence Null-background electrophysiology with L446F; humanized C. elegans STXBP1 variant panel with western blot and RT-PCR

    PMID:31855252 PMID:32073399 PMID:32112430

    Open questions at the time
    • Structural basis for L446F gain-of-function not determined
    • Whether gain-of-function and loss-of-function variants require different therapeutic strategies not addressed
  14. 2021 High

    Munc18-1 was shown to be uniquely required for dense-core vesicle (neuropeptide) exocytosis in CNS neurons, with no substitution by Munc18-2 or Munc18-3, extending the protein's essential role beyond synaptic vesicle fusion.

    Evidence Conditional Munc18-1 null neurons; single-vesicle pHluorin imaging of NPY and BDNF release; isoform rescue

    PMID:34103363

    Open questions at the time
    • Whether DCV secretion deficits contribute to STXBP1 encephalopathy phenotypes not tested
    • Mechanism for isoform specificity not resolved
  15. 2024 High

    Discovery of a physical interaction between STXBP1 and the phospholipase DDHD2 revealed an unexpected role in controlling plasma membrane lipid remodeling—specifically saturated free fatty acid generation during neuronal stimulation and memory acquisition—expanding STXBP1 function beyond SNARE-mediated fusion.

    Evidence Pulldown-mass spectrometry; DDHD2 KO and STXBP1+/- mice; lipidomics; behavioral memory assays

    PMID:38316990

    Open questions at the time
    • Whether DDHD2 interaction is direct or within a larger complex not confirmed by recombinant reconstitution
    • How lipid remodeling feeds back on SNARE-dependent exocytosis unknown
    • Relevance to STXBP1 encephalopathy not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of the fully assembled Munc18-1/Munc13-1/SNARE template complex, the precise mechanism by which Munc13 unfurls the domain 3a autoinhibitory loop, how STXBP1 gain-of-function mutations produce distinct clinical phenotypes from haploinsufficiency variants, and whether the DDHD2-dependent lipid remodeling pathway contributes to disease.
  • No high-resolution structure of the Munc18-1/Munc13-MUN/SNARE template intermediate
  • Therapeutic potential of chemical chaperones not validated in patient-derived neurons or clinical trials
  • Gain-of-function vs. loss-of-function variant-specific therapeutic strategies undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 5 GO:0044183 protein folding chaperone 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 5 GO:0031410 cytoplasmic vesicle 3 GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-162582 Signal Transduction 4 R-HSA-9609507 Protein localization 3
Partners
CDK5DDHD2GRM4SNAP25STX1ASYTL4UNC13AVAMP2
Complex memberships
Munc18-1/Munc13-1/SNARE template complexMunc18-1/SNARE core complexMunc18-1/syntaxin-1 binary complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 STXBP1 (n-Sec1/Munc18-1) was identified as a neural-specific syntaxin-binding protein; it binds syntaxin 1a, 2, and 3 but not syntaxin 4, and becomes membrane-associated in the presence of syntaxin 1a, implicating it in synaptic vesicle docking and fusion. Pulldown with syntaxin fusion proteins coupled to agarose beads; subcellular fractionation; RNA blot analysis Proceedings of the National Academy of Sciences of the United States of America High 8108429 8134339
1994 rbSec1 (rat brain STXBP1 homolog) specifically interacts with syntaxin but not with SNAP-25 or synaptobrevin/VAMP in brain detergent extracts, establishing that Sec1-family function in membrane fusion involves direct interaction with a t-SNARE. GST pulldown from Triton X-100 brain extract; Northern blot; immunoblot Proceedings of the National Academy of Sciences of the United States of America High 8134339
1996 Munc18-1 is phosphorylated by conventional PKC (Ca2+- and phospholipid-dependent) at Ser306 and Ser313 in a cell-free system; PKC-catalyzed phosphorylation inhibits Munc18-1 interaction with syntaxin, and the Munc18-1/syntaxin complex is not a PKC substrate, revealing a regulatory switch for synaptic vesicle docking/fusion. In vitro kinase assay with recombinant Munc18-1 and purified PKC; phosphorylation-site mapping; pulldown binding assay The Journal of biological chemistry High 8631738
2000 Endogenous presynaptic PKC isoforms phosphorylate Munc18-1 in nerve terminals in a Ca2+-dependent manner following depolarization; PKC activation inhibits synaptic Munc18-1 interaction with syntaxin-1A by ~50%, and constitutive phosphatase activity (PP1/PP2B) keeps basal phosphorylation low, defining a dynamic regulatory mechanism for neurotransmitter release. Phosphorylation assays in isolated rat brain nerve terminals with phorbol esters, PKC inhibitors, phosphatase inhibitors, and K+-evoked depolarization; immunoprecipitation of Munc18-1/syntaxin complexes The European journal of neuroscience High 10651895
2003 Munc18-1 Ser313 is phosphorylated in intact chromaffin cells (by histamine/Ca2+) and in synaptosomes (by depolarization/mGluR activation) in a PKC-dependent manner, with PP1 and PP2B as the dephosphorylating phosphatases, linking this phosphorylation to regulation of transmitter release kinetics. Phospho-Ser313-specific antisera; permeabilized chromaffin cells; intact synaptosomes with pharmacological stimulation; kinase/phosphatase inhibitor profiling Journal of neurochemistry High 12950453
2004 Munc18-1 co-purifies and co-localizes with neuronal cytoskeletal proteins (neurofilaments, microtubules) and with Cdk5; reciprocal immunoaffinity chromatography confirmed strong protein–protein interaction between Munc18-1, cytoskeletal elements, and Cdk5, suggesting a role in cytoskeletal dynamics. Munc18-1 immunoaffinity chromatography; immunofluorescence in PC12 cells; immunohistochemistry and immuno-electron microscopy in rat olfactory bulb Neurochemistry international Medium 12963086
2004 Munc18-1 and syntaxin-1A interact in living cells, as demonstrated by FRET; the interaction occurs first at the Golgi and then at the plasma membrane, syntaxin-1A trafficking to the plasma membrane depends on Munc18-1, and phosphomimetic mutations at Ser313 (PKC site) and Thr574 (Cdk5 site) reduce Munc18-1/syntaxin-1A interaction. FRET between CFP-Munc18-1 and citrine-YFP-syntaxin-1A in HEK293 and chromaffin cells; fluorescence lifetime imaging; syntaxin open/closed conformation mutants; phosphomimetic Munc18-1 mutants The Journal of biological chemistry High 15489225
1999 rbSec1 (STXBP1) prevents syntaxin-1A-induced blockade of Golgi-to-plasma-membrane traffic and Golgi disassembly in neurosecretion-incompetent cells, demonstrating that Munc18-1 interaction with syntaxin-1A is required not only for plasma membrane exocytosis but also for proper intracellular trafficking of syntaxin-1A. Transfection of syntaxin-1A ± rbSec1 in non-neurosecretory cells; immunofluorescence for Golgi markers; protein transport assays Journal of cell science Medium 10341206
2006 The linker domain of Slp4-a/granuphilin interacts directly with Munc18-1 and promotes docking of dense-core vesicles to the plasma membrane; despite increased docking, exocytosis is inhibited, identifying a Slp4-a/Munc18-1/syntaxin-1a ternary docking complex. Deletion/chimeric analysis; co-immunoprecipitation; TIRF-based exocytosis assays in PC12 cells Molecular biology of the cell Medium 16481396
2007 Munc18-1 interacts with neuronal SNAREs in two distinct modes: binding to isolated syntaxin-1 in a closed conformation, and binding to assembled SNARE complexes. Both modes involve the same low-affinity interaction with the extreme syntaxin-1 N-terminus, which links the two modes; disrupting the N-terminal syntaxin/Munc18 interaction with a competing peptide blocks neurotransmitter release at the calyx of Held synapse. Transfected cell in vitro assay; electrophysiology at calyx of Held (N-terminal peptide injection); co-immunoprecipitation; truncated syntaxin constructs The Journal of neuroscience : the official journal of the Society for Neuroscience High 17989281
2007 Binding of Munc18-1 to closed syntaxin-1 stimulates vesicle docking, while a distinct Munc18-1 interaction mode regulates the subsequent vesicle priming step in chromaffin cells; Munc18-1 null chromaffin cells show abolished vesicle docking and reduced syntaxin levels that are restored by Munc18-1 variants. Expression of Munc18 variants in Munc18-1 null chromaffin cells; electron microscopy for vesicle docking; capacitance recordings for exocytosis; syntaxin-1 immunoblot The Journal of neuroscience : the official journal of the Society for Neuroscience High 17687045
2007 Rab3a promotes secretory vesicle docking in chromaffin cells in a manner that requires Munc18-1; GTP- or GDP-locked Rab3a mutants fail to support docking, and wild-type Rab3a cannot promote docking in Munc18-1 null cells, placing Rab3a upstream of Munc18-1 in the docking cascade. Expression of Rab3a conformation-locked mutants in wild-type and munc18-1 null chromaffin cells; electron microscopy vesicle distribution analysis PloS one Medium 17637832
2008 S-nitrosylation of syntaxin 1a at Cys145 disrupts binding of Munc18-1 to the closed conformation of syntaxin 1a in vitro without affecting SNARE complex formation or Munc18-1/SNARE complex binding; nitrosomimetic Cys145 mutants alter Munc18-1 localization and exocytosis kinetics in cells. In vitro NO treatment; site-directed mutagenesis (C145S, nitrosomimetic mutants); Munc18-1 binding assays; live-cell imaging; carbon fiber amperometry The Biochemical journal High 18452404
2008 C. elegans UNC-18 (STXBP1 ortholog) acts as a molecular chaperone for syntaxin-1 (UNC-64) in neurons, promoting its anterograde ER-to-plasma-membrane transport; this chaperone function requires both closed-syntaxin binding and N-terminal syntaxin binding modes, while N-terminal binding is especially important for locomotion behavior. unc-18 mutant analysis; colocalization with ER markers; carbohydrate modification assays for ER retention; double mutants disrupting syntaxin binding modes; behavioral assays Molecular biology of the cell High 18596236
2009 Presynaptic metabotropic glutamate receptor 4 (mGluR4) binds Munc18-1 at resting Ca2+ levels and releases it upon Ca2+-calmodulin activation; sequestration of Munc18-1 by mGluR4 suppresses basal synaptic vesicle release, and release of Munc18-1 from mGluR4 mediates paired-pulse facilitation. Co-immunoprecipitation; Ca2+-binding assay (EC50 determination); permeabilized PC12 cell secretion assay; electrophysiology (paired-pulse facilitation); mGluR4 domain peptide experiments Proceedings of the National Academy of Sciences of the United States of America High 19822743
2010 Munc18-1 binds directly to synaptobrevin (VAMP2) and to the SNARE four-helix bundle with low-micromolar affinity through the same cavity that binds syntaxin-1; the Munc18-1 binding site on synaptobrevin is at the C-terminus of its SNARE motif, placing Munc18-1 at the site of membrane fusion. NMR; isothermal titration calorimetry; fluorescence anisotropy; analytical ultracentrifugation — multiple biophysical approaches Biochemistry High 20102228
2010 The SNARE four-helix bundle and the syntaxin N-peptide constitute a minimal complement for Munc18-1 activation of membrane fusion; the syntaxin Habc domain is dispensable for Munc18-1 stimulation of fusion, and the central cavity of Munc18-1 is required for fusion stimulation. Reconstituted membrane fusion assay; Munc18-1 and syntaxin domain deletion mutants; liposome fusion The Journal of cell biology High 20603329
2010 Munc18-1 stimulates neuronal SNARE-mediated membrane fusion via its interaction with the SNARE core even when both the Habc domain and N-peptide of syntaxin are absent, as shown by single-vesicle FRET fusion assay and EPR analysis of SNARE core/Munc18 interaction. Single-molecule FRET vesicle fusion assay; electron paramagnetic resonance (EPR) ACS chemical neuroscience High 20300453
2011 Munc18-1 modulates fusion pore properties via distinct interactions: the R39C mutation (disrupting syntaxin-1 binding) and P242S (disrupting Mint interaction) stabilize narrow fusion pores and increase fusion event amplitude; wild-type Munc18-1 abrogates synaptobrevin2/syntaxin-1 binary trans-complex formation, providing a proofreading function that favors vesicle tethering to preformed syntaxin-SNAP-25 binary cis-complexes. Patch-clamp capacitance recordings; STED microscopy; single-molecule atomic force microscopy; transfection of Munc18-1 mutants in lactotrophs The Journal of neuroscience : the official journal of the Society for Neuroscience High 21677188
2011 Munc18-1 inhibition of membrane fusion requires syntaxin-1 in a closed conformation; concurrent incubation with VAMP2 liposomes and SNAP-25 releases the inhibition and stimulates fusion specifically for VAMP2 (not VAMP8), requiring N-terminal syntaxin binding for robust stimulation, demonstrating Munc18-1 as a stage-specific off/on switch. Reconstituted sequential t-SNARE/v-SNARE assembly assay; liposome lipid mixing assay; temperature-controlled incubations; SNARE and Munc18-1 mutants The Journal of biological chemistry High 21730064
2011 Munc18-1 dual roles (chaperone of syntaxin-1A vs. SNARE complex activation) rely on distinct binding modes of its central cavity; a novel cavity mutant shows reduced syntaxin-1A binding and impaired chaperone function while retaining SNARE complex binding and ability to stimulate liposome fusion and secretion in neuroendocrine cells. Site-directed mutagenesis; co-immunoprecipitation; liposome fusion assay; secretion assay in neuroendocrine cells Molecular biology of the cell High 21900493
2012 Vesicle docking by synaptotagmin-1 is a prerequisite for Munc18-1 to accelerate trans-SNARE (SNAREpin) assembly and membrane fusion in a reconstituted giant unilamellar vesicle system; Munc18-1 was positioned as central to a sequential cascade: docking → priming → fusion. Reconstituted giant unilamellar vesicle docking/fusion assay with synaptotagmin-1, Munc18-1, complexin II, and Ca2+ The Journal of biological chemistry High 22810233
2013 Domain 3a of Munc18-1 plays a crucial role in vesicle priming (downstream of docking) independently of its syntaxin-1 chaperoning activity; insertion mutations in domain 3a abolish secretion rescue while fully restoring syntaxin-1 plasma membrane expression and vesicle docking, and these mutants show impaired binding to the assembled SNARE complex. Munc18-1 null/knockdown PC12 cell rescue with domain 3a insertion mutants; exocytosis assay; electron microscopy for vesicle docking; SNARE complex binding assays Journal of cell science High 23525015
2013 The Munc18-1 domain 3a loop (residues 317-333) is essential for neuroexocytosis but dispensable for syntaxin-1A chaperoning and plasma membrane delivery; deletion of this loop fully rescues syntaxin-1A transport but not secretory granule fusion, and reduces SNARE complex binding at the cell surface. Munc18-1 deletion mutant (Δ317-333) expressed in DKD-PC12 cells; exocytosis assay; immunofluorescence; in vitro binding Journal of cell science High 23761923
2013 Munc18-1 allosterically controls syntaxin-1a conformational exchange between closed and open states; EPR shows that Munc18-1 binding shifts syntaxin H3 toward the ordered, folded state, suppresses the minor open population, and narrows H3-Habc distance distributions. Electron paramagnetic resonance (EPR) spectroscopy on spin-labeled syntaxin; membrane-reconstituted full-length syntaxin ± Munc18-1 Biophysical journal High 23561535
2014 Disease-linked Munc18-1 C180Y mutation renders the protein unstable at 37°C (but functional at permissive temperature), and undergoes K48-linked polyubiquitination leading to proteasomal (not lysosomal) degradation; mutant protein retains t-SNARE chaperone function but cannot support neuroexocytosis, which is rescued at lower temperature. Temperature-sensitive exocytosis assay in Munc18-null PC12 cells; ubiquitination assay; proteasome/lysosome inhibitor experiments; in vitro stability assay Cell reports High 25284778
2014 Munc18-1 rapidly redistributes from synapses during stimulation and reclusters within minutes; reclustering is independent of syntaxin-1 but requires Ca2+ influx and PKC activity; a PKC-insensitive Munc18-1 mutant fails to recluster; synaptic Munc18-1 levels correlate with synaptic strength and releasable vesicle pool size. FRAP on fluorescently tagged endogenous Munc18-1 knock-in mouse neurons; PKC inhibitors; Ca2+ chelation; PKC phosphorylation site mutant The Journal of cell biology High 24590174
2014 Pro335 in Munc18-1 domain 3a plays a pivotal role balancing syntaxin-1 chaperoning vs. exocytic priming functions; P335A mutation reduces syntaxin-1 binding but enhances exocytosis rescue, while combination with flanking mutations abolishes both functions; the hinged/extended helix conformation controls the balance. Site-directed mutagenesis of domain 3a residues; rescue of exocytosis and syntaxin-1 expression in Munc18-1/2 double-knockdown PC12 cells; pulldown binding assays The Journal of biological chemistry High 25326390
2015 Heterozygous STXBP1 loss-of-function mutations reduce Munc18-1 protein levels by ~30% and also reduce its binding partner Syntaxin-1 by ~30%, decreasing spontaneous and evoked neurotransmitter release by ~50% in isogenic human ES cell-derived neurons. Conditional heterozygous/homozygous STXBP1 knockin human ES cells; human neuron differentiation; immunoblot; electrophysiology (spontaneous and evoked release) The Journal of clinical investigation High 26280581
2015 The trans-SNARE-regulating function of Munc18-1 (promoting SNARE complex zippering) is essential for both spontaneous and evoked neurotransmitter release in neurons; v-SNARE mutations that selectively impair Munc18-1's ability to promote trans-SNARE zippering strongly inhibit release; and an Ohtahara Syndrome-associated Munc18-1 mutation compromises this trans-SNARE-regulating function. Reconstituted SNARE zippering assay; cultured neuron electrophysiology with v-SNARE mutants; disease variant analysis Nature communications High 26572858
2016 Extension of helix 12 in Munc18-1 domain 3a is required for vesicle priming but not docking or syntaxin-1 chaperoning; gain-of-function P335A mutation (extended helix) markedly increases priming and secretory amplitude, while disruptive mutations (L348R, Δ324-339) reduce priming; effects are consistent in chromaffin cells and in an in vitro fusion assay. Expression of Munc18-1 helix-12 mutants in null chromaffin cells; capacitance recordings; electron microscopy; in vitro fusion assay The Journal of neuroscience : the official journal of the Society for Neuroscience High 27358447
2016 The Munc18-1 domain 3a hinge-loop controls syntaxin-1A nanodomain assembly and single-molecule dynamics; upon stimulation, wild-type Munc18-1 mobility increases while syntaxin-1A becomes less mobile (confinement); hinge-loop deletion (Δ317-333) blocks both diffusional switches and prolongs vesicle docking, establishing the loop as a conformational switch coupling Munc18-1 to syntaxin-1A SNARE complex assembly during priming. Single-molecule tracking of Munc18-1 and syntaxin-1A; TIRF microscopy; electron microscopy for docking; BoNT/E control The Journal of cell biology High 27646276
2017 Munc18-1 is autoinhibited in its synaptobrevin-binding activity via a 'furled conformation' of a loop; D326K mutation disrupting this conformation enhances specific synaptobrevin binding and stimulates Munc18-1 activity in Munc18-1/Munc13-1-dependent reconstitution assays, enables Munc13-1-independent fusion, and produces gain-of-function in C. elegans unc-18 nulls; conversely, L348R inhibits binding and activity. NMR (specific vs. non-specific synaptobrevin binding); reconstituted membrane fusion assay (with/without Munc13-1); C. elegans rescue experiments with gain/loss-of-function mutants eLife High 28477408
2017 Tyrosine phosphorylation of Munc18-1 at Y473 by neuronal Src family kinases abolishes its SNARE-templating activity and prevents vesicle priming (but not docking) in hippocampal null neurons; the mechanism involves occlusion of the synaptobrevin/VAMP2 binding groove and hindrance of domain 3a conformational changes. Phosphomimetic Y473D mutant; in vitro SNARE complex formation assay; hippocampal munc18-1 null neuron rescue; electrophysiology; high-frequency stimulation rescue The EMBO journal High 29150433
2017 Munc18-1/UNC-18 primes vesicle fusion downstream of Munc13-1/UNC-13 by templating SNARE complex assembly; UNC-18 P334A (gain-of-function) partially bypasses UNC-13 requirement, and this bypass is synergistically augmented by tom-1 (tomosyn) null mutation; P335A Munc18-1 shows enhanced SNARE complex formation and SNARE complex binding in vitro. C. elegans behavioral and electrophysiology assays; mammalian neuron electrophysiology; liposome fusion assay; biochemical SNARE assembly assays The Journal of neuroscience : the official journal of the Society for Neuroscience High 28821673
2018 At least five disease-linked Munc18-1 missense mutations cause protein destabilization and aggregation; mutant Munc18-1 aggregates sequester wild-type Munc18-1, depleting functional protein beyond hemizygous levels; chemical chaperones (4-phenylbutyrate, sorbitol, trehalose) reverse these deficits in vitro and in vivo in yeast, C. elegans, and mouse neurons. S. cerevisiae, C. elegans, and conditional Munc18-1 KO mouse neurons; aggregation assays; western blot; behavioral rescue; chemical chaperone treatment Nature communications High 30266908
2018 STXBP1 disease variants have severely decreased protein stability; heterozygous STXBP1 mutations do not reduce exocytosis when overexpressed on a heterozygous background, indicating haploinsufficiency (not dominant-negative) as the primary cellular mechanism; GABAergic neuron-specific Stxbp1 haploinsufficiency causes cortical hyperexcitability. Allelic series of seven STXBP1 mutants in null and heterozygous mouse neurons; EEG recordings in four mouse models; c-Fos staining; conditional GABAergic neuron-specific knockout Brain : a journal of neurology High 29538625
2019 The MUN domain of Munc13-1 stabilizes the Munc18-1/syntaxin-1/VAMP2 template complex by ~2.1 kBT, as measured by single-molecule force spectroscopy; this MUN-bound template complex enhances SNAP-25 binding and full SNARE assembly; mutational disruption of the complex impairs SNARE assembly and neurotransmitter release. Single-molecule force spectroscopy; mutagenesis of MUN-template interface; SNARE assembly assay; neurotransmitter release assay Proceedings of the National Academy of Sciences of the United States of America High 31888993
2020 Stxbp1 haploinsufficiency specifically reduces cortical inhibitory neurotransmission from both parvalbumin-expressing and somatostatin-expressing interneurons via distinct mechanisms, contributing to cortical hyperexcitability and seizures in mice. Stxbp1+/- mouse; in vivo EEG; whole-cell patch clamp of inhibitory synaptic transmission; conditional interneuron-specific knockouts; behavioral assays eLife High 32073399
2020 A homozygous Munc18-1 L446F mutation causes a gain-of-function in synaptic transmission (2-fold increased evoked release probability) with minor impact on protein stability compared to heterozygous disease mutants, demonstrating that STXBP1 mutations can produce divergent cellular effects (loss vs. gain of function) leading to different clinical features. Patch clamp recordings in Munc18-1 null mouse neurons expressing L446F; protein stability assays; morphological analysis Brain : a journal of neurology High 31855252
2020 STXBP1 protein variants associated with epilepsy in humanized C. elegans unc-18 null strains show reduced protein levels (20-30% of wild-type) despite normal mRNA levels, indicating that the mutations cause protein instability rather than transcriptional defects. CRISPR/Cas9 unc-18 null rescue with human STXBP1 variants; behavioral assays; electrophysiology; western blot; RT-PCR Epilepsia High 32112430
2021 Munc18-1 is essential specifically for neuropeptide/dense-core vesicle (DCV) secretion in CNS neurons; MUNC18-2 and MUNC18-3 cannot substitute; heterozygous Munc18-1 reduction impairs DCV exocytosis especially during initial high-frequency stimulation. Conditional Munc18-1 null neurons; pHluorin/mCherry-tagged NPY and BDNF single-vesicle imaging; action potential train stimulation; rescue with MUNC18-1/2/3 The Journal of neuroscience : the official journal of the Society for Neuroscience High 34103363
2024 STXBP1 physically interacts with the phospholipase A1 enzyme DDHD2 (via pulldown-mass spectrometry); STXBP1 controls DDHD2 targeting to the plasma membrane and the generation of saturated free fatty acids (especially myristic acid C14:0) in the brain during neuronal stimulation and memory acquisition. Pulldown-mass spectrometry; DDHD2 knockout mice; STXBP1+/- haploinsufficient mice; lipidomics; behavioral memory assays; STXBP1/2 knockout neurosecretory cells The EMBO journal High 38316990

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 n-Sec1: a neural-specific syntaxin-binding protein. Proceedings of the National Academy of Sciences of the United States of America 366 8108429
2016 STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. Neurology 238 26865513
1994 A rat brain Sec1 homologue related to Rop and UNC18 interacts with syntaxin. Proceedings of the National Academy of Sciences of the United States of America 234 8134339
1996 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. The Journal of biological chemistry 222 8631738
2014 GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology 209 24623842
2007 Munc18-1 in secretion: lonely Munc joins SNARE team and takes control. Trends in neurosciences 152 17956762
2010 Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. Neurology 136 20876469
2009 De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy. Annals of neurology 125 19557857
2007 Dual modes of Munc18-1/SNARE interactions are coupled by functionally critical binding to syntaxin-1 N terminus. The Journal of neuroscience : the official journal of the Society for Neuroscience 118 17989281
2016 TNFα induces co-trafficking of TRPV1/TRPA1 in VAMP1-containing vesicles to the plasmalemma via Munc18-1/syntaxin1/SNAP-25 mediated fusion. Scientific reports 104 26888187
1993 The C. elegans unc-18 gene encodes a protein expressed in motor neurons. Neuron 101 8398155
2011 Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations. Epilepsia 99 21770924
2007 Munc18-1: sequential interactions with the fusion machinery stimulate vesicle docking and priming. The Journal of neuroscience : the official journal of the Society for Neuroscience 99 17687045
2018 Protein instability, haploinsufficiency, and cortical hyper-excitability underlie STXBP1 encephalopathy. Brain : a journal of neurology 88 29538625
2022 Assessing the landscape of STXBP1-related disorders in 534 individuals. Brain : a journal of neurology 85 35190816
2011 STXBP1-related encephalopathy presenting as infantile spasms and generalized tremor in three patients. Epilepsia 83 21762454
2010 SNARE bundle and syntaxin N-peptide constitute a minimal complement for Munc18-1 activation of membrane fusion. The Journal of cell biology 83 20603329
2010 Binding of Munc18-1 to synaptobrevin and to the SNARE four-helix bundle. Biochemistry 81 20102228
1999 Blockade of membrane transport and disassembly of the Golgi complex by expression of syntaxin 1A in neurosecretion-incompetent cells: prevention by rbSEC1. Journal of cell science 79 10341206
2011 Intellectual disability without epilepsy associated with STXBP1 disruption. European journal of human genetics : EJHG 77 21364700
2020 STXBP1 encephalopathies: Clinical spectrum, disease mechanisms, and therapeutic strategies. Journal of neurochemistry 76 32643187
2016 Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish. PloS one 75 26963117
2017 Autoinhibition of Munc18-1 modulates synaptobrevin binding and helps to enable Munc13-dependent regulation of membrane fusion. eLife 69 28477408
2010 Munc18-1 as a key regulator of neurosecretion. Journal of neurochemistry 63 20681955
2019 Munc13-1 MUN domain and Munc18-1 cooperatively chaperone SNARE assembly through a tetrameric complex. Proceedings of the National Academy of Sciences of the United States of America 62 31888993
2015 Analysis of conditional heterozygous STXBP1 mutations in human neurons. The Journal of clinical investigation 62 26280581
2020 Stxbp1/Munc18-1 haploinsufficiency impairs inhibition and mediates key neurological features of STXBP1 encephalopathy. eLife 61 32073399
2018 Mechanism-based rescue of Munc18-1 dysfunction in varied encephalopathies by chemical chaperones. Nature communications 60 30266908
2000 Dynamics of munc18-1 phosphorylation/dephosphorylation in rat brain nerve terminals. The European journal of neuroscience 60 10651895
2011 Munc18-1 tuning of vesicle merger and fusion pore properties. The Journal of neuroscience : the official journal of the Society for Neuroscience 59 21677188
2008 UNC-18 promotes both the anterograde trafficking and synaptic function of syntaxin. Molecular biology of the cell 59 18596236
2006 The Slp4-a linker domain controls exocytosis through interaction with Munc18-1.syntaxin-1a complex. Molecular biology of the cell 59 16481396
2004 Trophic support delays but does not prevent cell-intrinsic degeneration of neurons deficient for munc18-1. The European journal of neuroscience 55 15255974
2008 S-nitrosylation of syntaxin 1 at Cys(145) is a regulatory switch controlling Munc18-1 binding. The Biochemical journal 53 18452404
2012 Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A. Genetics in medicine : official journal of the American College of Medical Genetics 52 22722545
2013 Early epileptic encephalopathies associated with STXBP1 mutations: Could we better delineate the phenotype? European journal of medical genetics 50 24189369
2015 The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis. Nature communications 49 26572858
2013 Reduction of seizure frequency after epilepsy surgery in a patient with STXBP1 encephalopathy and clinical description of six novel mutation carriers. Epilepsia 48 23409955
2003 Physiological regulation of Munc18/nSec1 phosphorylation on serine-313. Journal of neurochemistry 47 12950453
2020 Homozygous STXBP1 variant causes encephalopathy and gain-of-function in synaptic transmission. Brain : a journal of neurology 46 31855252
2015 Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases. Epilepsia 46 26514728
2016 Extension of Helix 12 in Munc18-1 Induces Vesicle Priming. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 27358447
2015 Loss of Munc18-1 long splice variant in GABAergic terminals is associated with cognitive decline and increased risk of dementia in a community sample. Molecular neurodegeneration 43 26628003
2004 Fluorescence resonance energy transfer reports properties of syntaxin1a interaction with Munc18-1 in vivo. The Journal of biological chemistry 43 15489225
2010 Single-Vesicle Fusion Assay Reveals Munc18-1 Binding to the SNARE Core Is Sufficient for Stimulating Membrane Fusion. ACS chemical neuroscience 41 20300453
2019 STXBP1 encephalopathy: Connecting neurodevelopmental disorders with α-synucleinopathies? Neurology 40 31221716
2009 The functions of Munc18-1 in regulated exocytosis. Annals of the New York Academy of Sciences 40 19161378
2016 Mislocalization of syntaxin-1 and impaired neurite growth observed in a human iPSC model for STXBP1-related epileptic encephalopathy. Epilepsia 39 26918652
2013 The Munc18-1 domain 3a loop is essential for neuroexocytosis but not for syntaxin-1A transport to the plasma membrane. Journal of cell science 39 23761923
2009 Abrogating Munc18-1-SNARE complex interaction has limited impact on exocytosis in PC12 cells. The Journal of biological chemistry 38 19483085
2016 The Munc18-1 domain 3a hinge-loop controls syntaxin-1A nanodomain assembly and engagement with the SNARE complex during secretory vesicle priming. The Journal of cell biology 37 27646276
2015 A de-novo STXBP1 gene mutation in a patient showing the Rett syndrome phenotype. Neuroreport 37 25714420
2014 Munc18-1 redistributes in nerve terminals in an activity- and PKC-dependent manner. The Journal of cell biology 36 24590174
2017 Germline and somatic mutations in STXBP1 with diverse neurodevelopmental phenotypes. Neurology. Genetics 35 29264391
2020 Functional analysis of epilepsy-associated variants in STXBP1/Munc18-1 using humanized Caenorhabditis elegans. Epilepsia 34 32112430
2012 SNAREpin assembly by Munc18-1 requires previous vesicle docking by synaptotagmin 1. The Journal of biological chemistry 34 22810233
2007 The role of Rab3a in secretory vesicle docking requires association/dissociation of guanidine phosphates and Munc18-1. PloS one 34 17637832
2017 UNC-18 and Tomosyn Antagonistically Control Synaptic Vesicle Priming Downstream of UNC-13 in Caenorhabditis elegans. The Journal of neuroscience : the official journal of the Society for Neuroscience 33 28821673
2015 Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation. Brain & development 33 26212315
2014 A novel de novo STXBP1 mutation is associated with mitochondrial complex I deficiency and late-onset juvenile-onset parkinsonism. Neurogenetics 33 25418441
2021 STXBP1 Syndrome Is Characterized by Inhibition-Dominated Dynamics of Resting-State EEG. Frontiers in physiology 32 35002760
2017 Munc18-1 haploinsufficiency impairs learning and memory by reduced synaptic vesicular release in a model of Ohtahara syndrome. Molecular and cellular neurosciences 31 29217410
2010 Paternal mosaicism of an STXBP1 mutation in OS. Clinical genetics 31 21062273
2017 Tyrosine phosphorylation of Munc18-1 inhibits synaptic transmission by preventing SNARE assembly. The EMBO journal 30 29150433
2012 A novel STXBP1 mutation causes focal seizures with neonatal onset. Journal of child neurology 30 22596016
2011 Resolving the function of distinct Munc18-1/SNARE protein interaction modes in a reconstituted membrane fusion assay. The Journal of biological chemistry 30 21730064
2019 Pathogenic Variants in STXBP1 and in Genes for GABAa Receptor Subunities Cause Atypical Rett/Rett-like Phenotypes. International journal of molecular sciences 29 31344879
2017 STXBP1 as a therapeutic target for epileptic encephalopathy. Expert opinion on therapeutic targets 29 28971703
2014 Increased polyubiquitination and proteasomal degradation of a Munc18-1 disease-linked mutant causes temperature-sensitive defect in exocytosis. Cell reports 29 25284778
2013 Allosteric control of syntaxin 1a by Munc18-1: characterization of the open and closed conformations of syntaxin. Biophysical journal 29 23561535
2004 Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins. Neurochemistry international 29 12963086
2011 Munc18-1 and Munc18-2 proteins modulate beta-cell Ca2+ sensitivity and kinetics of insulin exocytosis differently. The Journal of biological chemistry 28 21690086
2017 Potentiation of excitatory synaptic transmission ameliorates aggression in mice with Stxbp1 haploinsufficiency. Human molecular genetics 27 29040524
2014 A pivotal role for pro-335 in balancing the dual functions of Munc18-1 domain-3a in regulated exocytosis. The Journal of biological chemistry 27 25326390
2009 Ca2+-dependent release of Munc18-1 from presynaptic mGluRs in short-term facilitation. Proceedings of the National Academy of Sciences of the United States of America 27 19822743
1999 nSec-1 (munc-18) interacts with both primed and unprimed syntaxin 1A and associates in a dimeric complex on adrenal chromaffin granules. The Biochemical journal 26 10477283
2023 Delineating clinical and developmental outcomes in STXBP1-related disorders. Brain : a journal of neurology 25 38015929
2016 Epilepsy is not a mandatory feature of STXBP1 associated ataxia-tremor-retardation syndrome. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 25 27184330
2013 Domain 3a of Munc18-1 plays a crucial role at the priming stage of exocytosis. Journal of cell science 25 23525015
2018 De novo mutations of STXBP1 in Chinese children with early onset epileptic encephalopathy. Genes, brain, and behavior 24 29896790
2017 Protein structure and phenotypic analysis of pathogenic and population missense variants in STXBP1. Molecular genetics & genomic medicine 23 28944233
2011 Dual roles of Munc18-1 rely on distinct binding modes of the central cavity with Stx1A and SNARE complex. Molecular biology of the cell 23 21900493
2024 The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids. The EMBO journal 22 38316990
2013 Neonatal suppression-burst without epileptic seizures: expanding the electroclinical phenotype of STXBP1-related, early-onset encephalopathy. Epileptic disorders : international epilepsy journal with videotape 22 23531706
2004 Amblyomma americanum salivary gland homolog of nSec1 is essential for saliva protein secretion. Biochemical and biophysical research communications 22 15504350
2023 Altered synaptic connectivity in an in vitro human model of STXBP1 encephalopathy. Brain : a journal of neurology 20 36315647
2022 Neuronal SNARE complex assembly guided by Munc18-1 and Munc13-1. FEBS open bio 20 35278279
2015 Synaptotagmin-1 is an antagonist for Munc18-1 in SNARE zippering. The Journal of biological chemistry 19 25716321
2003 Role of Munc18-1 in synaptic vesicle and large dense-core vesicle secretion. Biochemical Society transactions 19 12887319
2021 Munc18-1 Is Essential for Neuropeptide Secretion in Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 18 34103363
2018 Bi-Allelic Mutations in STXBP2 Reveal a Complementary Role for STXBP1 in Cytotoxic Lymphocyte Killing. Frontiers in immunology 18 29599780
2012 PKC-2 phosphorylation of UNC-18 Ser322 in AFD neurons regulates temperature dependency of locomotion. The Journal of neuroscience : the official journal of the Society for Neuroscience 18 22593072
2005 The role of Munc18-1 in docking and exocytosis of peptide hormone vesicles in the anterior pituitary. Biology of the cell 18 15898951
2019 STXBP1 encephalopathy is associated with awake bruxism. Epilepsy & behavior : E&B 17 30654231
2018 Munc18-2, but not Munc18-1 or Munc18-3, controls compound and single-vesicle-regulated exocytosis in mast cells. The Journal of biological chemistry 17 29599294
2012 Munc18-1 controls SNARE protein complex assembly during human sperm acrosomal exocytosis. The Journal of biological chemistry 17 23091057
2011 Structure-function study of mammalian Munc18-1 and C. elegans UNC-18 implicates domain 3b in the regulation of exocytosis. PloS one 17 21445306
2022 Clemizole and trazodone are effective antiseizure treatments in a zebrafish model of STXBP1 disorder. Epilepsia open 16 35451230
2022 Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy. Molecular therapy : the journal of the American Society of Gene Therapy 15 35283272
2013 Folinic acid responsive epilepsy in Ohtahara syndrome caused by STXBP1 mutation. Pediatric neurology 15 24315539