Affinage

STXBP1

Syntaxin-binding protein 1 · UniProt P61764

Length
594 aa
Mass
67.6 kDa
Annotated
2026-06-10
100 papers in source corpus 60 papers cited in narrative 60 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STXBP1 (Munc18-1) is a neural-specific Sec1/Munc18 (SM) protein that serves as the master organizer of regulated exocytosis, controlling synaptic vesicle and dense-core vesicle fusion through sequential, physically distinct engagements with the SNARE machinery (PMID:8108429, PMID:8134339, PMID:17687045, PMID:34103363). It first acts as a molecular chaperone for syntaxin-1, binding the closed conformation, stabilizing the protein and extending its half-life, and directing it to the plasma membrane; loss of Munc18-1 reduces syntaxin-1 levels and mistargets it to perinuclear compartments (PMID:10648557, PMID:15935055, PMID:18077557). Through its domain-1 cleft, closed-syntaxin binding drives vesicle docking, while a separable activity centered on domain 3a (helix 12 and the hinge-loop) engages the assembling SNARE bundle to mediate vesicle priming (PMID:17687045, PMID:21193638, PMID:27358447, PMID:27646276). Mechanistically, Munc18-1 templates SNARE assembly by forming an obligate intermediate that juxtaposes the N-terminal SNARE motifs of syntaxin-1 and VAMP2/synaptobrevin while holding their C-termini apart, permitting SNAP-25 binding to drive full zippering; the MUN domain of Munc13-1 stabilizes this template complex, and Munc18-1 binding overcomes αSNAP-mediated inhibition of fusion (PMID:30540253, PMID:31888993, PMID:33055194, PMID:31548544). This catalytic activity positions Munc18-1 downstream of synaptotagmin-dependent docking and upstream of trans-SNARE zippering (PMID:22810233, PMID:26572858). Its activity is tuned by phosphorylation: conventional PKC phosphorylates Ser306/Ser313 to reduce syntaxin affinity and potentiate vesicle pool replenishment and post-tetanic potentiation, Src-family kinases phosphorylate Y473 to abolish SNARE templating, and ERK-mediated phosphorylation downstream of CB1R/mGluR signaling triggers ubiquitin-proteasome degradation (PMID:8631738, PMID:16997485, PMID:24520164, PMID:29150433, PMID:27056679). De novo and missense STXBP1 mutations cause early infantile epileptic encephalopathy, acting predominantly through protein destabilization and haploinsufficiency — and in some cases dominant-negative aggregation that co-sequesters wild-type protein — which reduces neurotransmission, with inhibitory GABAergic and neuropeptide signaling particularly affected (PMID:18469812, PMID:26280581, PMID:29538625, PMID:30266908, PMID:32073399). Beyond core exocytosis, Munc18-1 chaperones α-synuclein to limit its aggregation, controls DDHD2 plasma-membrane targeting and saturated fatty acid production for memory, and is required for cortical neuron radial migration and neuronal survival (PMID:27597756, PMID:38316990, PMID:29191246, PMID:28348137).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1994 High

    Established that the neural protein Munc18-1 is a selective syntaxin-binding partner, placing it at the heart of synaptic vesicle docking and fusion rather than acting generally across the SNARE machinery.

    Evidence GST pulldowns from brain extract showing binding to syntaxin-1/2/3 but not syntaxin-4, SNAP-25, or VAMP, plus syntaxin-dependent membrane association

    PMID:8108429 PMID:8134339

    Open questions at the time
    • Did not define the syntaxin conformation bound
    • No functional consequence for fusion established
  2. 1996 High

    Demonstrated functional conservation and isoform specificity of Munc18-1 in neurotransmitter release, and identified PKC phosphorylation as a regulatory switch on syntaxin binding.

    Evidence Transgenic rescue of C. elegans unc-18 null by neural (but not ubiquitous) Munc18; in vitro PKC phosphorylation at Ser306/Ser313 with binding assays

    PMID:8631738 PMID:8824310

    Open questions at the time
    • In vivo physiological relevance of the phosphosites not yet shown
    • Step in exocytosis controlled by phosphorylation unresolved
  3. 2000 High

    Resolved that Munc18-1 binds a closed conformation of syntaxin-1 mutually exclusive with ternary SNARE assembly, framing the central puzzle of how a SNARE-blocking protein could promote fusion.

    Evidence In vitro binding, nondenaturing gels, neurotoxin treatment, cross-linking of brain membranes; nerve-terminal phosphorylation assays

    PMID:10648557 PMID:10651895

    Open questions at the time
    • Mechanism reconciling SNARE inhibition with positive fusion role unknown
    • Did not address binding to assembled SNAREs
  4. 2001 High

    Provided in vivo genetic proof that Munc18-1 is required for vesicle docking and exocytosis, converting a binding partner into a functionally essential exocytic factor.

    Evidence Electron microscopy docking assay and patch-clamp capacitance in munc18-1 null chromaffin cells, plus overexpression

    PMID:11545717

    Open questions at the time
    • Whether docking and a later priming step are separable not resolved
    • Molecular basis of docking defect unclear
  5. 2005 High

    Identified syntaxin-1 chaperoning/stabilization as an upstream Munc18-1 function, explaining how loss of Munc18-1 collapses the presynaptic SNARE pool.

    Evidence Pulse-chase in HEK293 cells and immunoblotting in munc18-1 KO mice; PC12 knockdown with rescue showing syntaxin-1 membrane targeting

    PMID:15935055 PMID:18077557

    Open questions at the time
    • Whether chaperoning fully accounts for downstream phenotypes debated
    • Trafficking route of syntaxin-1 not fully defined
  6. 2007 High

    Discovered a second binding mode — Munc18-1 binding to assembled SNARE complexes via the syntaxin N-peptide — and dissociated closed-syntaxin-dependent docking from a distinct priming activity.

    Evidence NMR and pulldowns on reconstituted SNARE complexes; Munc18 variant rescue with capacitance and EM in null chromaffin cells

    PMID:17301226 PMID:17687045

    Open questions at the time
    • Precise contribution of each binding mode to fusion not quantified
    • Structural basis of the priming activity unresolved
  7. 2009 High

    Mapped SNARE-complex binding (open syntaxin) to vesicle priming specifically, and confirmed in vivo that syntaxin N-terminus binding is essential for neurotransmission.

    Evidence Lentiviral rescue with separation-of-function mutants in munc18-1 KO neurons; C. elegans rescue with N-terminus and closed-syntaxin binding mutants; PC12 double-KD rescue

    PMID:19032153 PMID:19255244 PMID:19812250

    Open questions at the time
    • Relative importance of N-peptide vs closed-syntaxin binding contested across systems
    • Direct fusion-catalysis mechanism still inferred
  8. 2010 High

    Defined the minimal molecular determinants of Munc18-1 fusion stimulation, including direct binding to synaptobrevin/VAMP2 through the same central cavity, advancing toward a catalytic templating model.

    Evidence NMR, ITC, fluorescence anisotropy on VAMP2 binding; reconstituted liposome fusion with syntaxin domain mapping; domain-1 cleft mutant analysis

    PMID:20102228 PMID:20603329 PMID:21193638

    Open questions at the time
    • How simultaneous syntaxin and VAMP2 engagement is coordinated unresolved
    • Order of events during fusion not yet established
  9. 2012 High

    Positioned Munc18-1 in the fusion pathway downstream of synaptotagmin docking and upstream of SNAREpin zippering, and linked disease mutations to protein instability.

    Evidence Reconstituted giant unilamellar vesicle fusion with ordered component addition; separation-of-function mutant rescue in KO neurons; disease-variant expression in N2a cells with NMD analysis

    PMID:20887364 PMID:22446389 PMID:22810233

    Open questions at the time
    • Contradiction over whether SNARE-complex binding is required for fusion (vs. #19) unresolved here
    • In vivo ordering not directly tested
  10. 2013 Medium

    Localized the priming-specific function to domain 3a, demonstrating mutants that fully chaperone syntaxin-1 and support docking yet abolish secretion.

    Evidence Domain 3a insertion mutant (K332E/K333E) rescue in PC12 double-KD cells with secretion, immunofluorescence, EM docking, and SNARE binding assays

    PMID:23525015

    Open questions at the time
    • Single lab, single cell system
    • Structural mechanism of helix 12 action not defined here
  11. 2014 High

    Showed Munc18-1 phosphorylation is dynamically regulated during synaptic plasticity and degradation, and extended its exocytic role to non-neuronal secretion.

    Evidence Gene replacement at the calyx of Held with phospho-mutants and electrophysiology; knock-in fluorescent Munc18-1 FRAP; proteomic identification of STXBP1 in Weibel-Palade body exocytosis; K48 ubiquitination assays

    PMID:24520164 PMID:24590174 PMID:24700782 PMID:25284778

    Open questions at the time
    • Kinase/phosphatase identities for some events not fully resolved
    • E3 ligase mediating ubiquitination unidentified
  12. 2015 High

    Established that promotion of trans-SNARE/VAMP2 zippering is the essential Munc18-1 function, that helix 12 conformation controls priming, and that Munc18-1 drives neuropeptide DCV exocytosis.

    Evidence Reconstituted trans-SNARE assay with v-SNARE mutants and neuronal electrophysiology; helix-12 mutant rescue in null chromaffin cells with EM; conditional KO with single-vesicle neuropeptide secretion; isogenic human-neuron STXBP1 mutations

    PMID:26280581 PMID:26572858 PMID:27358447 PMID:34103363

    Open questions at the time
    • Atomic structure of the templating intermediate not yet captured
    • How helix 12 engages VAMP2 not yet defined here
  13. 2016 Medium

    Identified the helix 12/VAMP2 interaction and syntaxin nanodomain confinement as the structural basis of priming, and uncovered a chaperone role for Munc18-1 in controlling α-synuclein aggregation.

    Evidence EPR on reconstituted SNARE complexes; single-molecule tracking and super-resolution in PC12 KD cells; single-molecule and gene-edited cell co-aggregation assays

    PMID:26876096 PMID:27597756 PMID:27646276

    Open questions at the time
    • α-synuclein chaperone function from a single lab and outside the exocytic role
    • Direct structural snapshot of helix 12-VAMP2 still indirect
  14. 2017 High

    Defined autoinhibition of VAMP2 binding, identified Src/ERK phosphorylation as negative regulators coupling presynaptic receptors to Munc18-1 turnover, and revealed non-exocytic roles in cortical migration and neuronal survival.

    Evidence NMR + reconstitution + C. elegans rescue (autoinhibition); in vitro fusion and KO-neuron rescue with Y473D and ERK phospho-mutants; in utero electroporation knockdown imaging; conditional KO with Munc18-3 rescue dissecting Golgi/survival from exocytosis

    PMID:27056679 PMID:28348137 PMID:28477408 PMID:29150433 PMID:29191246

    Open questions at the time
    • In vivo significance of autoinhibition during synaptic signaling not fully mapped
    • Mechanism of Golgi/survival function independent of syntaxin unresolved
  15. 2018 High

    Provided direct single-molecule proof of the obligate template-complex mechanism of stepwise SNARE zippering and consolidated protein destabilization/aggregation as the unifying disease mechanism.

    Evidence Optical-tweezers single-molecule force spectroscopy with mutagenesis and SM-protein controls; allelic series of disease variants in null-background neurons with EEG; multi-organism aggregation models with chemical-chaperone rescue

    PMID:29538625 PMID:30266908 PMID:30540253

    Open questions at the time
    • Whether all disease variants act purely by instability vs additional dominant effects still being delineated
    • In vivo template-complex dynamics not directly observed
  16. 2019 High

    Showed Munc13-1's MUN domain energetically stabilizes the Munc18-1/SNARE template and that Munc18-1 must bind syntaxin-1 first to evade αSNAP inhibition, integrating the catalytic cascade.

    Evidence Single-molecule force spectroscopy measuring template stabilization; reconstituted liposome fusion with FRET and NMR mapping αSNAP inhibition

    PMID:31548544 PMID:31888993

    Open questions at the time
    • In vivo confirmation of the kBT stabilization effect lacking
    • How ordering of binding is enforced in cells unclear
  17. 2020 High

    Mapped the precise helix 11/12-VAMP2 interface required for templating, identified GABAergic interneuron dysfunction as central to STXBP1 encephalopathy, and characterized a gain-of-function disease allele.

    Evidence Unnatural-amino-acid crosslinking with reconstitution and KO-neuron rescue (Q301D); cell-type-specific conditional Stxbp1 KO with electrophysiology; humanized C. elegans variant panel; L446F null-background rescue

    PMID:31855252 PMID:32073399 PMID:32112430 PMID:33055194

    Open questions at the time
    • How gain-of-function alleles produce disease distinct from loss-of-function not fully resolved
    • Cell-type-specific circuit consequences in humans untested
  18. 2024 Medium

    Extended Munc18-1 function into lipid signaling for memory, showing it controls DDHD2 membrane targeting and saturated fatty acid production.

    Evidence Pulldown-mass spectrometry, STXBP1/2 KO neurosecretory cells and Stxbp1+/- mice, lipidomics, and memory behavioral assays

    PMID:38316990

    Open questions at the time
    • Single lab
    • Relationship between lipid function and core exocytic role not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • An atomic-resolution structure of the full Munc18-1/syntaxin-1/VAMP2/Munc13-1 templating intermediate in a membrane context, and a unified explanation of how diverse missense variants partition between loss-of-function instability, dominant-negative aggregation, and gain-of-function, remain to be established.
  • No membrane-embedded structure of the complete template complex
  • Genotype-to-mechanism mapping across the full variant spectrum incomplete
  • How non-exocytic functions (α-synuclein, DDHD2, migration) integrate with core role unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 4 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-112316 Neuronal System 3 R-HSA-1643685 Disease 3 R-HSA-9609507 Protein localization 3 R-HSA-1266738 Developmental Biology 2
Partners
DDHD2GRM4RAB3ASNAP25SNCASTX1AUNC13AVAMP2
Complex memberships
Munc18-1/SNARE/Munc13-1 MUN tetrameric complexMunc18-1/syntaxin-1/VAMP2 template complex

Evidence

Reading pass · 60 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 n-Sec1/STXBP1 is a neural-specific syntaxin-binding protein that 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. GST pulldown, subcellular fractionation, RNA blot analysis Proceedings of the National Academy of Sciences of the United States of America High 8108429 8134339
1994 rbSec1/STXBP1 specifically interacts with syntaxin but not with SNAP-25 or synaptobrevin/VAMP in brain extract pulldowns, establishing a selective t-SNARE interaction. GST fusion protein pulldown from Triton X-100 brain extract Proceedings of the National Academy of Sciences of the United States of America High 8134339
1996 Munc18-1/STXBP1 is phosphorylated by conventional PKC (Ca2+- and phospholipid-dependent) at Ser306 and Ser313; this phosphorylation inhibits its interaction with syntaxin. The Munc18-1 complexed with syntaxin is not phosphorylated. In vitro phosphorylation assay with recombinant Munc18-1, mutagenesis of phosphorylation sites, binding assay The Journal of biological chemistry High 8631738
1996 Mouse Munc18-1 (neural isoform) functionally rescues locomotion and cholinergic defects in C. elegans unc-18 null mutants, demonstrating evolutionary conservation of its role in neurotransmitter release; the ubiquitous Munc18-3 isoform fails to rescue. Transgenic rescue of C. elegans unc-18 null mutant, behavioral and pharmacological assays The Journal of neuroscience : the official journal of the Society for Neuroscience High 8824310
2000 nSec1/Munc18-1 binds a closed conformation of syntaxin 1A; association of nSec1 with syntaxin 1A prevents assembly of the ternary SNARE complex (with SNAP-25 and VAMP2), and conversely, SNARE complex formation precludes nSec1 binding. In vitro binding assays, nondenaturing gel electrophoresis, neurotoxin treatment, chemical cross-linking of rat brain membranes The Journal of cell biology High 10648557
2000 Synaptic Munc18-1 is dynamically phosphorylated by endogenous presynaptic PKC isoforms at nerve terminals; K+-evoked depolarization increases phosphorylation within 5 s in a Ca2+-dependent manner; phosphorylation inhibits interaction with syntaxin-1A by ~50%; PP1 and PP2B are the responsible phosphatases. Phosphorylation assays in isolated rat brain nerve terminals, PKC inhibitors, phosphatase inhibitors, immunoprecipitation The European journal of neuroscience High 10651895
2001 Munc18-1 is required for docking of large dense-core vesicles (LDCVs) to the plasma membrane; munc18-1 null chromaffin cells show a 10-fold reduction in morphologically docked LDCVs and a 10-fold reduction in Ca2+-dependent LDCV exocytosis; acute Munc18-1 overexpression increases releasable vesicles and accelerates vesicle supply. Electron microscopy morphological docking assay, patch-clamp capacitance measurements in munc18-1 null mouse chromaffin cells, overexpression in bovine chromaffin cells Neuron High 11545717
2003 Munc18-1/nSec1 Ser-313 is physiologically phosphorylated in intact chromaffin cells and synaptosomes in response to depolarization and receptor activation; PKC is the kinase and PP1/PP2B are the phosphatases responsible. Phospho-Ser-313-specific antisera in intact/permeabilized chromaffin cells and synaptosomes, kinase/phosphatase inhibitors Journal of neurochemistry Medium 12950453
2004 Munc18-1 co-purifies with and co-localizes with Cdk5 and neuronal cytoskeletal proteins (neurofilaments, microtubules) in rat brain, suggesting a protein-protein interaction; cytoskeletal proteins and Cdk5 co-purify with Munc18-1 in immunoaffinity chromatography. Immunoaffinity chromatography, immunofluorescence, immunohistochemistry, immuno-electron microscopy Neurochemistry international Low 12963086
2004 Cell-specific deletion of munc18-1 in cerebellar Purkinje cells causes specific loss of those neurons in vivo, demonstrating a cell-intrinsic function of Munc18-1 essential for prolonged neuronal survival independent of synaptic activity. Conditional Cre-lox cell-specific knockout in vivo, histology The European journal of neuroscience Medium 15255974
2004 Munc18-1 mutants with wild-type syntaxin binding can alter kinetics of individual exocytotic release events and have reduced Mint (Mints) binding affinity, indicating syntaxin-independent functions via interactions with Mint proteins. Chromaffin cell overexpression, amperometry, binding affinity assays with Munc18-1 mutants Molecular biology of the cell Medium 15563604
2005 Munc18-1 directly promotes the stability of syntaxin-1 (pulse-chase analysis shows Munc18-1 increases syntaxin-1 half-life); syntaxin-1 levels are reduced 70% in munc18-1 KO mice; however, residual syntaxin-1 still correctly targets to synapses and forms SDS-resistant SNARE complexes. Pulse-chase analysis in transfected HEK293 cells, immunoblotting in munc18-1 KO mice Journal of neurochemistry High 15935055
2006 PKC phosphorylation of Munc18-1 at Ser313 potentiates vesicle pool replenishment after depleting stimulation (phosphomimetic S313D increases replenishment; non-phosphorylatable 3A mutant decreases it); vesicle docking is promoted by Munc18-1 in a phosphorylation-independent manner. Chromaffin cell overexpression with phosphomimetic and phospho-null Munc18-1 mutants, capacitance measurements, electron microscopy Neuroscience Medium 16997485
2007 Munc18-1 binds directly to assembled SNARE complexes containing syntaxin-1 (open conformation); this interaction involves the syntaxin-1 N-terminal Habc domain and the four-helical SNARE bundle. Munc18-1 thus has two distinct binding modes: to closed syntaxin-1 and to assembled SNARE complexes. In vitro binding assays (NMR, pulldowns), reconstituted SNARE complex Proceedings of the National Academy of Sciences of the United States of America High 17301226
2007 Binding of Munc18-1 to closed syntaxin-1 conformation stimulates vesicle docking; a distinct interaction mode (not closed syntaxin binding) regulates the subsequent vesicle priming step; Munc18-2 rescues docking but not priming in munc18-1 null chromaffin cells. Munc18 variant expression in munc18-1 null chromaffin cells, capacitance measurements, electron microscopy The Journal of neuroscience : the official journal of the Society for Neuroscience High 17687045
2007 Munc18-1 is critical for plasma membrane localization of syntaxin-1 in PC12 cells; knockdown of Munc18-1 causes syntaxin-1 mislocalization to perinuclear regions (co-localizing with dense-core vesicle marker) without affecting SNAP-25 localization; reintroduction of Munc18-1 restores syntaxin-1 plasma membrane targeting. Stable knockdown cell lines, immunofluorescence, vesicle docking assay, secretion assay Molecular biology of the cell High 18077557
2008 S-nitrosylation of syntaxin-1a at Cys145 disrupts Munc18-1 binding to the closed conformation of syntaxin-1a in vitro; a non-nitrosylatable C145S mutant resists this effect; NO does not inhibit SNARE complex formation or Munc18-1 binding to assembled SNARE complexes; nitrosomimetic syntaxin-1a expression in cells affects Munc18-1 localization and alters exocytosis kinetics and quantal size. In vitro binding assays, site-directed mutagenesis, live-cell exocytosis assay, molecular dynamics simulations The Biochemical journal High 18452404
2008 Munc18-1 directly interacts with Rab3A; a gain-of-function E466K mutation (based on yeast Sly1p) increases this interaction, stimulates exocytosis, and increases secretory granule density at the cell periphery; the stimulatory effects require binding to closed syntaxin-1. Co-immunoprecipitation, exocytosis assays in chromaffin/PC12 cells, confocal microscopy, gain-of-function mutant analysis The Biochemical journal Medium 17919117
2008 De novo mutations in STXBP1 identified in patients with early infantile epileptic encephalopathy; mutant proteins are thermolabile compared to wild type (CD melting experiments) and show impaired binding to syntaxin, indicating that haploinsufficiency (protein instability + reduced syntaxin binding) underlies disease. Circular dichroism melting experiments, binding assays with mutant proteins, genomic sequencing Nature genetics High 18469812
2009 Munc18-1 binding to SNARE complexes (open syntaxin-1) mediates synaptic vesicle priming but not Ca2+-triggered fusion; point mutations preserving closed syntaxin-1 binding but disrupting SNARE complex binding selectively impair priming; Munc18-1 and complexin-1 bind simultaneously to SNARE complexes. Lentiviral rescue in munc18-1 KO neurons, point mutagenesis, electrophysiology The Journal of cell biology High 19255244
2009 Binding of UNC-18 (C. elegans STXBP1 ortholog) to the N-terminus of syntaxin (UNC-64) is essential for neurotransmission in vivo; UNC-18(F113R) defective in N-terminus binding fails to rescue unc-18 null locomotion defects, whereas UNC-18(R39C) defective in closed syntaxin binding fully rescues. Transgenic rescue of C. elegans unc-18 null mutant with point mutants, behavioral assays The Biochemical journal High 19032153
2009 Presynaptic mGluR4 binds Munc18-1 in a Ca2+-dependent manner (EC50 ~168 nM for Ca2+); Ca2+-activated calmodulin disrupts the mGluR4-Munc18-1 interaction, releasing Munc18-1 to facilitate vesicle release; this mechanism contributes to paired-pulse facilitation. Co-immunoprecipitation, permeabilized PC12 cell secretion assay, synaptic transmission recordings, Ca2+ titration Proceedings of the National Academy of Sciences of the United States of America Medium 19822743
2009 Rescue experiments in Munc18-1/-2 double knockdown PC12 cells show that binding to the closed conformation of syntaxin-1 is essential for Munc18-1's stimulatory action on syntaxin-1 expression, localization, and secretion; binding to the syntaxin-1 N-terminus plays a more limited role. Double knockdown with siRNA, rescue with Munc18-1 point mutants (K46E/E59K; F115E/E132A), secretion assays, immunofluorescence Molecular biology of the cell High 19812250
2010 Munc18-1 binds to synaptobrevin and to the SNARE four-helix bundle with similar low micromolar affinity; both interactions involve the same cavity of Munc18-1 that binds syntaxin-1; the binding site on synaptobrevin is at the C-terminus of its SNARE motif. NMR spectroscopy, fluorescence anisotropy, ITC, sedimentation assays 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 Habc domain of syntaxin is not required for Munc18-1-stimulated fusion; the central cavity region of Munc18-1 is required for fusion stimulation. Reconstituted liposome fusion assay, syntaxin deletion and mutant analysis The Journal of cell biology High 20603329
2010 Munc18-1 domain-1 cleft mutations that reduce syntaxin-1 binding correlate tightly with impaired syntaxin-1 chaperoning, reduced dense-core vesicle docking, and reduced secretion; priming mutant phenotypes can largely be explained by reduced syntaxin-1 chaperoning. Munc18-1/-2 double knockdown rescue with domain-1 mutants, vesicle docking (EM), secretion assays, binding assays Proceedings of the National Academy of Sciences of the United States of America Medium 21193638
2011 Munc18-1 domain-1 cleft is essential for syntaxin-1 binding, chaperoning, vesicle docking, and secretion; correlations between binding and all downstream functions support a unified mechanism whereby syntaxin-1 chaperoning by domain-1 is the primary upstream function. Munc18-1/-2 double KD rescue with seven domain-1 mutants, binding assays, EM docking, secretion assays Molecular biology of the cell Medium 21900502
2011 Munc18-1 performs a proofing function by inhibiting VAMP2/synaptobrevin tethering to monomeric syntaxin-1 at the plasma membrane (wild-type Munc18-1 abrogates Syb2-Synt1 binary trans-complex interaction at single-molecule level); Munc18-1 favors vesicle tethering to preformed syntaxin1A-SNAP25B binary cis-complexes. Single-molecule AFM force spectroscopy, patch-clamp capacitance, STED microscopy, chromaffin cell overexpression The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 21677188
2011 In reconstituted liposome fusion assay, Munc18-1 inhibition (via closed syntaxin) is released by concurrent incubation with VAMP2 liposomes and SNAP-25, specifically requiring Munc18-1/VAMP2 interaction; Munc18-1 binding to syntaxin N-peptide is obligatory for robust stimulation of fusion but not for inhibitory function. Reconstituted liposome fusion assay with defined mutants and isoform controls The Journal of biological chemistry High 21730064
2012 Munc18-1 point mutations that strongly impair binding to free syntaxin-1 N-terminus and to assembled SNARE complexes support normal docking, priming, and fusion of synaptic vesicles and normal synaptic plasticity in munc18-1 null neurons. Lentiviral rescue in munc18-1 KO neurons, electrophysiology, electron microscopy The EMBO journal High 22446389
2012 In reconstituted giant unilamellar vesicle system, synaptotagmin-1-mediated vesicle docking is a prerequisite for Munc18-1 to accelerate trans-SNARE complex (SNAREpin) assembly and membrane fusion; Munc18-1 positions itself downstream of synaptotagmin docking and upstream of SNAREpin zippering. Reconstituted giant unilamellar vesicle fusion assay with sequential addition of components The Journal of biological chemistry High 22810233
2012 STXBP1 disease variants with missense mutations show protein degradation in neuroblastoma2A cells (reduced protein levels), consistent with protein instability as the primary pathogenic mechanism; nonsense-mediated mRNA decay also demonstrated for splicing mutations. Transient expression in neuroblastoma2A cells, Western blot, RNA analysis in lymphoblastoid cells Epilepsia Medium 20887364
2012 Munc18-1 controls SNARE complex assembly during human sperm acrosomal exocytosis; inactivation of endogenous Munc18-1 with antibody prevents trans-SNARE complex stabilization and inhibits acrosomal exocytosis; recombinant Munc18-1 blocks secretion by sequestering monomeric syntaxin. Function-blocking antibody, recombinant protein addition, electron microscopy, SNARE complex formation assay The Journal of biological chemistry Medium 23091057
2013 Domain 3a insertion mutants of Munc18-1 (K332E/K333E) completely lose ability to rescue secretion but effectively restore syntaxin-1 expression, plasma membrane localization, and vesicle docking; these mutants show impaired SNARE complex binding, identifying domain 3a as critical for the priming step specifically. Munc18-1/-2 double KD rescue with insertion mutants, secretion assay, immunofluorescence, EM docking, binding assay Journal of cell science Medium 23525015
2014 STXBP1 promotes Weibel-Palade body exocytosis in endothelial cells through interaction with Rab27A effector Slp4-a; STXBP1 interacts with syntaxin-2 and -3 but not syntaxin-4; STXBP1 haploinsufficiency in patient-derived cells impairs histamine- and forskolin-stimulated VWF secretion. Proteomic screen for Slp4-a targets, co-immunoprecipitation, siRNA knockdown, patient-derived blood outgrowth endothelial cells, VWF secretion assay Blood High 24700782
2014 Munc18-1 is a dynamically regulated PKC target during post-tetanic potentiation (PTP); two PKC phosphorylation sites of Munc18-1 are critically important for PTP at the calyx of Held synapse; a phosphatase limits PTP duration; a conventional PKC isoform initiates PTP. Gene replacement strategy at calyx of Held, electrophysiology, pharmacological kinase/phosphatase inhibition eLife High 24520164
2014 Munc18-1 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. Knock-in mouse with fluorescently tagged Munc18-1 from endogenous locus, FRAP in hippocampal neurons, pharmacological manipulation The Journal of cell biology High 24590174
2015 Heterozygous STXBP1 loss-of-function mutations in human neurons reduce Munc18-1 protein and syntaxin-1 levels by ~30% and decrease spontaneous and evoked neurotransmitter release by ~50%, confirming a presynaptic impairment mechanism. Conditional heterozygous/homozygous STXBP1 mutations in human ES cell-derived neurons, electrophysiology The Journal of clinical investigation High 26280581
2015 The trans-SNARE-regulating function of Munc18-1 (promoting VAMP2 zippering) is essential for synaptic exocytosis; v-SNARE mutations that selectively impair Munc18-1's ability to promote trans-SNARE zippering strongly inhibit neurotransmitter release; an Ohtahara Syndrome-associated Munc18-1 mutation compromises this trans-SNARE-regulating function. Reconstituted trans-SNARE assay, lentiviral expression of v-SNARE mutants in cultured neurons, electrophysiology Nature communications High 26572858
2015 Munc18-1 domain 3a helix 12 conformation controls vesicle priming; disruptive mutations (L348R, Δ324-339) reduce priming and secretory amplitude; gain-of-function P335A (extends helix) markedly increases priming; effects are specific to priming with unchanged fusion kinetics and Ca2+ dependence. Expression of helix-12 mutants in Munc18-1 null chromaffin cells, capacitance measurements, EM, in vitro fusion assay The Journal of neuroscience : the official journal of the Society for Neuroscience High 27358447
2015 Munc18-1 is essential for neuropeptide secretion from dense-core vesicles; conditional inactivation abolishes all DCV exocytosis; Munc18-2 and Munc18-3 cannot substitute; heterozygous Munc18-1 impairs DCV exocytosis especially during peak stimulation. Conditional KO in mouse CNS neurons, single-vesicle pHluorin-tagged neuropeptide Y/BDNF secretion assay during action potential trains The Journal of neuroscience : the official journal of the Society for Neuroscience High 34103363
2016 Munc18-1 is a molecular chaperone for α-synuclein that controls its self-replicating aggregation; disease-linked EIEE Munc18-1 mutants form polymers that co-aggregate wild-type Munc18-1 and α-synuclein, forming Lewy body-like structures; removal of endogenous Munc18-1 increases α-synuclein aggregation propensity, rescued by Munc18-1 WT re-expression. Single-molecule analysis, gene-edited cells, primary neurons, co-aggregation assays, confocal microscopy The Journal of cell biology Medium 27597756
2016 The Munc18-1 domain 3a hinge-loop (residues 317-333) controls syntaxin-1A confinement into nanodomains and engagement with the SNARE complex during priming; a deletion mutant (Δ317-333) prolongs vesicle docking and blocks stimulation-induced diffusional changes of Munc18-1 and syntaxin-1A in nanodomains. Single-molecule tracking, super-resolution microscopy, PC12 double KD rescue, secretion assay The Journal of cell biology Medium 27646276
2016 Munc18-1 domain 3a helix 12 interacts with synaptobrevin-2/VAMP2 to mediate SNARE complex formation and vesicle priming; EPR spectroscopy shows Munc18-1 shifts syntaxin/SNAP-25 complex from inhibitory 2:1 to productive 1:1 open-state configuration. Electron paramagnetic resonance (EPR) spectroscopy on reconstituted SNARE complexes Structure (London, England : 1993) Medium 26876096
2016 All disease-causing STXBP1 variants tested have severely decreased protein levels, indicating impaired protein stability as the primary molecular defect; disease variants support synaptic transmission to variable extent on null background but show no dominant-negative effect on heterozygous background. Allelic series of STXBP1 variants in null-background neurons, Western blot, electrophysiology, four mouse models Brain : a journal of neurology High 29538625
2017 Munc18-1 has autoinhibition of synaptobrevin binding via a 'furled conformation' loop; a D326K mutation disrupting this autoinhibition stimulates Munc18-1 activity in reconstitution assays and causes gain-of-function in C. elegans; an L348R mutation inhibiting synaptobrevin binding reduces activity; this autoinhibition helps enable Munc13-1-dependent regulation. NMR spectroscopy, reconstitution assays (Munc18-1 + Munc13-1 dependent fusion), C. elegans rescue experiments eLife High 28477408
2017 Tyrosine phosphorylation of Munc18-1 at Y473 by Src family kinases abolishes its SNARE-templating stimulatory function and membrane fusion in vitro, and disrupts vesicle priming (but not docking) in munc18-1 null neurons; non-phosphorylatable Munc18-1 supports normal transmission; ERK-dependent Munc18-1 phosphorylation leads to its degradation by the ubiquitin-proteasome system. In vitro fusion assay, munc18-1 KO neuron rescue with Y473D mutant, electrophysiology, mass spectrometry phospho-proteomics The EMBO journal High 29150433
2017 CB1R and mGluR2/3 activation induces presynaptic inhibition through ERK-mediated phosphorylation of Munc18-1, causing decreased synaptic transmission and subsequent ubiquitin-proteasome-dependent Munc18-1 degradation; preventing ERK-dependent Munc18-1 phosphorylation increases synaptic strength. Gene replacement with phospho-mutant Munc18-1, pharmacological ERK/MEK inhibition, electrophysiology The EMBO journal Medium 27056679
2017 Munc18-1 knockdown impairs radial migration of cortical neurons during corticogenesis; Syntaxin1A is critical for radial migration downstream of Munc18-1; Munc18-1 knockdown hampers post-Golgi vesicle trafficking and plasma membrane vesicle fusion in vivo and in vitro. In utero electroporation knockdown, time-lapse imaging, cortical neuron fractionation, vesicle trafficking assay Acta neuropathologica communications Medium 29191246
2018 Munc18-1 catalyzes stepwise zippering of synaptic SNAREs (syntaxin, VAMP2, SNAP-25) via an obligate template complex intermediate; Munc18-1 juxtaposes N-terminal SNARE motif regions of syntaxin and VAMP2 while keeping C-terminal regions separated; SNAP-25 then binds to induce full zippering; mutations modulating template complex stability correspondingly affect membrane fusion; SM proteins Munc18-3 and Vps33 similarly chaperone SNARE assembly. Single-molecule force spectroscopy (optical tweezers), mutagenesis, reconstitution assays eLife High 30540253
2018 At least five disease-linked missense mutations of Munc18-1 destabilize and aggregate the mutant protein; mutant aggregates incorporate wild-type Munc18-1, depleting functional protein below hemizygous levels (dominant-negative aggregation mechanism); chemical chaperones (4-phenylbutyrate, sorbitol, trehalose) reverse these deficits in vitro and in vivo. In vitro aggregation assays, S. cerevisiae strains, C. elegans models, conditional KO mouse neurons, Western blot Nature communications High 30266908
2019 Munc18-1 is crucial to overcome αSNAP inhibition of synaptic vesicle fusion; αSNAP inhibits liposome fusion by binding syntaxin-1 (blocking Munc18-1 binding), by binding syntaxin-1-SNAP-25 heterodimers (blocking SNARE formation), and by binding trans-SNARE complexes; inhibition is avoided only when Munc18-1 binds syntaxin-1 first, leading to Munc18-1-Munc13-1-dependent fusion. Liposome fusion assays, FRET, NMR spectroscopy Nature communications High 31548544
2019 MUN domain of Munc13-1 stabilizes the Munc18-1/SNARE template complex by ~2.1 kBT, forming a tetrameric complex; this stabilization enhances SNAP-25 binding and full SNARE assembly; mutational studies confirm functional importance for neurotransmitter release. Single-molecule force spectroscopy (optical tweezers), mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 31888993
2020 Stxbp1 haploinsufficiency reduces cortical inhibitory neurotransmission via distinct mechanisms from parvalbumin-expressing and somatostatin-expressing interneurons; GABAergic synaptic dysfunction is a crucial contributor to STXBP1 encephalopathy pathogenesis. Heterozygous Stxbp1 mouse model, cell-type-specific Cre lines, patch-clamp electrophysiology, behavioral assays eLife High 32073399
2020 Homozygous STXBP1 L446F mutation causes a gain-of-function: 2-fold increase in evoked synaptic transmission and release probability with reduced paired-pulse plasticity; protein stability is less severely affected than typical heterozygous disease mutants. Munc18-1 null neuron rescue with L446F, patch-clamp electrophysiology, Western blot Brain : a journal of neurology Medium 31855252
2020 Helices 11 and 12 of Munc18-1 domain 3a interact with VAMP2 SNARE motif (layers -4 to +5); Q301 in helix 11 is pivotal for VAMP2 binding and template complex formation; Q301D mutant fails to stimulate membrane fusion in reconstituted assay; Munc13-1 cannot bypass requirement for Munc18-1/VAMP2 interaction; Q301D expression in Munc18-1 deficient neurons severely reduces synaptic transmission. Site-specific crosslinking with unnatural amino acid, reconstituted vesicle fusion assay, lentiviral rescue in KO neurons, electrophysiology eNeuro High 33055194
2020 All eight epilepsy-associated STXBP1 missense variants tested in humanized C. elegans show reduced protein levels (20-30% of wild-type) consistent with protein instability; locomotion and electrophysiological deficits vary by variant; no difference in mRNA levels confirming post-transcriptional instability. CRISPR/Cas9 unc-18 null C. elegans rescued with human STXBP1 variants, behavioral assays, electrophysiology, Western blot Epilepsia High 32112430
2014 Munc18-1 undergoes K48-linked polyubiquitination leading to proteasomal (not lysosomal) degradation; the C180Y disease-causing mutation greatly potentiates polyubiquitination and proteasomal degradation, rendering Munc18-1 unable to support neuroexocytosis; this phenotype is reversed at permissive temperature. Ubiquitination assays, proteasome/lysosome inhibitors, temperature-shift rescue, secretion assays in Munc18-deficient cells Cell reports Medium 25284778
2017 Early cis-Golgi condensation is the first cellular abnormality upon Munc18-1 loss in neurons (before synaptogenesis); expression of Munc18-3 (which does not bind syntaxin-1) in Munc18-1 KO neurons prevents cell death and restores Golgi morphology but does not rescue synaptic transmission or syntaxin-1 targeting, indicating distinct cell-survival and exocytotic functions. Conditional KO neurons, immunofluorescence, electron microscopy, Munc18-3 rescue The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 28348137
2024 STXBP1 interacts with DDHD2 (a phospholipase A1); STXBP1 controls DDHD2 targeting to the plasma membrane and generation of saturated free fatty acids (myristic acid) in the brain; this interaction mediates long-term memory formation. Pulldown-mass spectrometry, STXBP1/2 knockout neurosecretory cells, Stxbp1+/- mouse model, lipidomic analysis, memory behavioral assays The EMBO journal Medium 38316990

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nature genetics 423 18469812
1994 n-Sec1: a neural-specific syntaxin-binding protein. Proceedings of the National Academy of Sciences of the United States of America 366 8108429
2001 Munc18-1 promotes large dense-core vesicle docking. Neuron 299 11545717
2007 Munc18-1 binds directly to the neuronal SNARE complex. Proceedings of the National Academy of Sciences of the United States of America 252 17301226
2016 STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. Neurology 242 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
2000 nSec1 binds a closed conformation of syntaxin1A. The Journal of cell biology 225 10648557
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
2009 Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming. The Journal of cell biology 128 19255244
2010 STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern. Epilepsia 120 20887364
2018 Munc18-1 catalyzes neuronal SNARE assembly by templating SNARE association. eLife 113 30540253
2011 Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations. Epilepsia 101 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
2022 Assessing the landscape of STXBP1-related disorders in 534 individuals. Brain : a journal of neurology 91 35190816
2018 Protein instability, haploinsufficiency, and cortical hyper-excitability underlie STXBP1 encephalopathy. Brain : a journal of neurology 90 29538625
2010 Possible roles for Munc18-1 domain 3a and Syntaxin1 N-peptide and C-terminal anchor in SNARE complex formation. Proceedings of the National Academy of Sciences of the United States of America 90 21193638
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
2020 STXBP1 encephalopathies: Clinical spectrum, disease mechanisms, and therapeutic strategies. Journal of neurochemistry 81 32643187
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
2016 Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish. PloS one 76 26963117
2015 Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis. eLife 76 26701912
2007 Munc18-1 is critical for plasma membrane localization of syntaxin1 but not of SNAP-25 in PC12 cells. Molecular biology of the cell 76 18077557
2005 Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation. Journal of neurochemistry 71 15935055
2009 Rescue of Munc18-1 and -2 double knockdown reveals the essential functions of interaction between Munc18 and closed syntaxin in PC12 cells. Molecular biology of the cell 70 19812250
2017 Autoinhibition of Munc18-1 modulates synaptobrevin binding and helps to enable Munc13-dependent regulation of membrane fusion. eLife 69 28477408
2013 Comparative studies of Munc18c and Munc18-1 reveal conserved and divergent mechanisms of Sec1/Munc18 proteins. Proceedings of the National Academy of Sciences of the United States of America 69 23918365
2020 Stxbp1/Munc18-1 haploinsufficiency impairs inhibition and mediates key neurological features of STXBP1 encephalopathy. eLife 64 32073399
2015 Analysis of conditional heterozygous STXBP1 mutations in human neurons. The Journal of clinical investigation 64 26280581
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 63 31888993
2010 Munc18-1 as a key regulator of neurosecretion. Journal of neurochemistry 63 20681955
2018 Mechanism-based rescue of Munc18-1 dysfunction in varied encephalopathies by chemical chaperones. Nature communications 62 30266908
2014 Munc18-1 is a dynamically regulated PKC target during short-term enhancement of transmitter release. eLife 62 24520164
2012 Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission. The EMBO journal 61 22446389
2012 Munc18-1 regulates first-phase insulin release by promoting granule docking to multiple syntaxin isoforms. The Journal of biological chemistry 61 22685295
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
2016 Munc18-1 is a molecular chaperone for α-synuclein, controlling its self-replicating aggregation. The Journal of cell biology 56 27597756
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
2011 Munc18-1 domain-1 controls vesicle docking and secretion by interacting with syntaxin-1 and chaperoning it to the plasma membrane. Molecular biology of the cell 52 21900502
2019 Munc18-1 is crucial to overcome the inhibition of synaptic vesicle fusion by αSNAP. Nature communications 50 31548544
2013 Early epileptic encephalopathies associated with STXBP1 mutations: Could we better delineate the phenotype? European journal of medical genetics 50 24189369
2004 Munc18-1 regulates early and late stages of exocytosis via syntaxin-independent protein interactions. Molecular biology of the cell 50 15563604
2015 The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis. Nature communications 49 26572858
2014 STXBP1 promotes Weibel-Palade body exocytosis through its interaction with the Rab27A effector Slp4-a. Blood 49 24700782
2006 Munc18-1 phosphorylation by protein kinase C potentiates vesicle pool replenishment in bovine chromaffin cells. Neuroscience 49 16997485
2008 A gain-of-function mutant of Munc18-1 stimulates secretory granule recruitment and exocytosis and reveals a direct interaction of Munc18-1 with Rab3. The Biochemical journal 48 17919117
2009 Binding of UNC-18 to the N-terminus of syntaxin is essential for neurotransmission in Caenorhabditis elegans. The Biochemical journal 47 19032153
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
2017 Early Golgi Abnormalities and Neurodegeneration upon Loss of Presynaptic Proteins Munc18-1, Syntaxin-1, or SNAP-25. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 28348137
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
2019 STXBP1 encephalopathy: Connecting neurodevelopmental disorders with α-synucleinopathies? Neurology 42 31221716
1996 A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 8824310
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
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 39 27646276
1998 Identification and characterization of the human ortholog of rat STXBP1, a protein implicated in vesicle trafficking and neurotransmitter release. Genomics 39 9545644
2016 Presynaptic inhibition upon CB1 or mGlu2/3 receptor activation requires ERK/MAPK phosphorylation of Munc18-1. The EMBO journal 38 27056679
2005 The syntaxin binding protein 1 gene (Stxbp1) is a candidate for an ethanol preference drinking locus on mouse chromosome 2. Alcoholism, clinical and experimental research 38 15897714
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
2021 STXBP1 Syndrome Is Characterized by Inhibition-Dominated Dynamics of Resting-State EEG. Frontiers in physiology 32 35002760
2016 Munc18-1 and the Syntaxin-1 N Terminus Regulate Open-Closed States in a t-SNARE Complex. Structure (London, England : 1993) 32 26876096
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
2023 Delineating clinical and developmental outcomes in STXBP1-related disorders. Brain : a journal of neurology 30 38015929
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
2011 Involvement of Rab3A in vesicle priming during exocytosis: interaction with Munc13-1 and Munc18-1. Traffic (Copenhagen, Denmark) 29 21689256
2004 Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins. Neurochemistry international 29 12963086
2017 MUNC18-1 gene abnormalities are involved in neurodevelopmental disorders through defective cortical architecture during brain development. Acta neuropathologica communications 28 29191246
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
2011 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. The international journal of neuropsychopharmacology 27 21669024
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
2013 Domain 3a of Munc18-1 plays a crucial role at the priming stage of exocytosis. Journal of cell science 25 23525015
2017 Protein structure and phenotypic analysis of pathogenic and population missense variants in STXBP1. Molecular genetics & genomic medicine 24 28944233
2024 The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids. The EMBO journal 22 38316990
2022 Neuronal SNARE complex assembly guided by Munc18-1 and Munc13-1. FEBS open bio 22 35278279
2013 Munc18-1 haploinsufficiency results in enhanced anxiety-like behavior as determined by heart rate responses in mice. Behavioural brain research 22 24304718
2004 Amblyomma americanum salivary gland homolog of nSec1 is essential for saliva protein secretion. Biochemical and biophysical research communications 22 15504350
2020 The Interaction of Munc18-1 Helix 11 and 12 with the Central Region of the VAMP2 SNARE Motif Is Essential for SNARE Templating and Synaptic Transmission. eNeuro 20 33055194
2016 Normal Molecular Specification and Neurodegenerative Disease-Like Death of Spinal Neurons Lacking the SNARE-Associated Synaptic Protein Munc18-1. The Journal of neuroscience : the official journal of the Society for Neuroscience 20 26758845
2021 Munc18-1 Is Essential for Neuropeptide Secretion in Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 19 34103363
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
2019 STXBP1 encephalopathy is associated with awake bruxism. Epilepsy & behavior : E&B 18 30654231
2012 Munc18-1 controls SNARE protein complex assembly during human sperm acrosomal exocytosis. The Journal of biological chemistry 18 23091057
2005 The role of Munc18-1 in docking and exocytosis of peptide hormone vesicles in the anterior pituitary. Biology of the cell 18 15898951

Missed literature

Know a paper Affinage missed for STXBP1? Flag it for the maintainers and the community.

No submissions yet.