Affinage

STXBP5

Syntaxin-binding protein 5 · UniProt Q5T5C0

Length
1151 aa
Mass
127.6 kDa
Annotated
2026-06-10
71 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STXBP5 (tomosyn-1) is a soluble inhibitory regulator of SNARE-mediated membrane fusion that acts as a presynaptic and secretory brake across neurons, neuroendocrine cells, beta-cells, platelets, endothelium, and immune cells (PMID:9620695, PMID:12782620, PMID:16895441). It was first identified as a syntaxin-1-binding protein that displaces Munc18 and assembles a non-fusogenic complex with syntaxin-1 and SNAP-25, reducing Ca2+-dependent exocytosis (PMID:9620695). Its C-terminal R-SNARE (VAMP-like) motif forms a genuine four-helical bundle SNARE core complex with syntaxin-1 and SNAP-25 that is structurally homologous to the synaptobrevin complex, competing with synaptobrevin/VAMP for t-SNARE binding to arrest fusion as a thermodynamic end product (PMID:12782620, PMID:15316007, PMID:25063806). A parallel and dominant inhibitory mechanism resides in the N-terminal WD40 β-propeller domain, which is required and sufficient to inhibit release by catalyzing oligomerization of SNARE complexes, and acts through assembly of the ternary tomosyn–syntaxin–SNAP25 complex at the plasma membrane (PMID:18936251, PMID:17666050, PMID:24782308). Functionally, tomosyn inhibits the priming/post-docking step rather than vesicle docking, limiting the readily releasable and primed vesicle pools without altering individual fusion kinetics (PMID:14983051, PMID:16895441, PMID:17881523). The tomosyn-SNARE arrest is reversed by NSF/α-SNAP disassembly, after which Munc18-1 scaffolding and Munc13-1 catalysis assemble fusogenic synaptobrevin-containing complexes, defining tomosyn and Munc18/Munc13 as antagonistic regulators of SNARE assembly (PMID:28821673, PMID:29485200). This inhibitory activity is dynamically de-repressed by phosphorylation via PKA, Akt, Cdk5, and PKCδ and by SUMO-2/3 modification, each of which relieves syntaxin binding to promote secretion, while phosphorylation-dependent HRD1-mediated ubiquitin-proteasomal degradation controls tomosyn abundance (PMID:16186257, PMID:25725259, PMID:27807164, PMID:28325894, PMID:29970602, PMID:25002582, PMID:29269412). Tomosyn engages tissue-specific t-SNAREs—syntaxin-4/SNAP-23 in adipocytes to inhibit insulin-stimulated GLUT4 translocation, syntaxin-11/SNAP-23 in platelet granule secretion, and syntaxin-4 in endothelial Weibel-Palade body exocytosis—and Stxbp5 knockout impairs platelet secretion, hemostasis, and thrombosis (PMID:12832401, PMID:25244094, PMID:25244095, PMID:32851733). Beyond its canonical exocytic role, tomosyn suppresses RhoA GTPase activity via its WD40 domain to maintain dendritic arborization, spine stability, and surface AMPA receptor expression, with ASD-associated WD40 variants showing loss of this function (PMID:32133675), and its SNARE-independent function in dense-core vesicle cargo packaging at the Golgi controls intracellular DCV cargo levels (PMID:37695731).

Mechanistic history

Synthesis pass · year-by-year structured walk · 29 steps
  1. 1998 High

    Established tomosyn as a syntaxin-1-binding protein, answering how an exocytic inhibitor could intercept the core fusion machinery by displacing Munc18 and forming an alternative syntaxin complex.

    Evidence Co-immunoprecipitation, biochemical fractionation, and overexpression-based exocytosis assay in PC12 cells

    PMID:9620695

    Open questions at the time
    • Did not resolve which tomosyn domain mediates inhibition
    • Mechanism of fusion arrest at the molecular level unresolved
  2. 2003 High

    Defined the molecular basis of inhibition by showing the C-terminal R-SNARE motif forms a bona fide four-helical SNARE complex that competes with synaptobrevin and is reversible by NSF/α-SNAP.

    Evidence In vitro reconstitution, CD spectroscopy, plasma membrane sheet competition, NSF disassembly assay, and PC12 capacitance measurements

    PMID:12782620

    Open questions at the time
    • Did not establish the contribution of the N-terminal domain
    • Step in the secretory pathway inhibited not yet mapped
  3. 2004 High

    Resolved the atomic structure of the tomosyn SNARE complex and showed both tomosyn and synaptobrevin complexes are mutually exclusive thermodynamic end products with impaired complexin binding.

    Evidence 2.0 Å X-ray crystallography with CD kinetics and displacement assays

    PMID:15316007

    Open questions at the time
    • Structure of the WD40 domain not determined
    • Did not address how the arrested complex is recycled in vivo
  4. 2004 High

    Localized tomosyn's action to the vesicle priming step, showing it reduces fusion-competent vesicles in a calcium-tunable manner without affecting docking.

    Evidence Capacitance, amperometry, EM, and calcium ramp experiments in chromaffin cells

    PMID:14983051

    Open questions at the time
    • Molecular mechanism of calcium-dependent relief of inhibition unresolved
  5. 2003 High

    Extended tomosyn's t-SNARE repertoire beyond neurons by showing it binds syntaxin-4/SNAP-23 and inhibits insulin-stimulated GLUT4 translocation in adipocytes.

    Evidence Yeast two-hybrid, in vitro binding, co-IP, and GFP-GLUT4 translocation imaging in 3T3-L1 adipocytes

    PMID:12832401

    Open questions at the time
    • Endogenous loss-of-function effect not tested in this study
    • How Munc18c integrates with the tomosyn complex unresolved
  6. 2006 High

    Provided in vivo genetic proof that tomosyn (C. elegans TOM-1) is an endogenous negative regulator of synaptic vesicle priming, complementing prior overexpression data.

    Evidence Electrophysiology, EM ultrastructure, and tom-1;unc-13 genetic epistasis in C. elegans

    PMID:16895441

    Open questions at the time
    • Domain requirements not dissected genetically here
  7. 2005 High

    Identified PKA phosphorylation as a physiological switch that relieves syntaxin binding to enhance the releasable pool and neurotransmitter release, linking tomosyn to PACAP-mediated facilitation.

    Evidence In vitro kinase assay, co-IP, electrophysiology, and PKA pharmacology in SCG neurons

    PMID:16186257

    Open questions at the time
    • Phosphorylation sites not mapped in this study
  8. 2007 High

    Resolved that tomosyn uses a dual inhibitory mechanism: the WD40 domain catalyzes SNARE complex oligomerization while the VAMP-like domain sequesters syntaxin, with the WD40 domain alone sufficient to inhibit release.

    Evidence Neuronal microinjection of domain truncations, co-IP oligomerization assay, and tomosyn-KO mouse analysis; corroborated by chromaffin cell domain-deletion capacitance mapping

    PMID:17666050 PMID:18936251

    Open questions at the time
    • Structural basis of WD40-driven oligomerization unresolved
    • How the two mechanisms are coordinated temporally unknown
  9. 2007 High

    Showed tomosyn inhibition extends to dense-core vesicle/neuropeptide release and is dynamically recruited to the membrane by RhoA/ROCK-dependent translocation upon stimulation.

    Evidence tom-1;unc-31 genetic epistasis with EM and neuropeptide assays; FRET/translocation imaging with ROCK inhibition and LPA in chromaffin/PC12 cells

    PMID:17545156 PMID:17881523

    Open questions at the time
    • Direct ROCK substrate site on syntaxin/tomosyn not fully defined
  10. 2006 Medium

    Demonstrated tomosyn negatively regulates insulin granule exocytosis at a post-docking step in beta-cells, generalizing the brake function to endocrine secretion.

    Evidence Co-IP, bidirectional overexpression/siRNA, AFM binding-force measurement, and EM docked-granule counting in beta-cells

    PMID:16505218 PMID:16787939

    Open questions at the time
    • Single-lab functional data
    • Physiological regulation of beta-cell tomosyn not addressed here
  11. 2011 High

    Identified the paralog tomosyn-2 (STXBP5L) as a genetically validated negative regulator of insulin secretion whose abundance is set by allele-specific proteasomal degradation.

    Evidence Positional cloning, in vitro binding, INS1 secretion assay, proteasomal degradation assay, and sub-congenic mouse islet phenotyping

    PMID:21998599

    Open questions at the time
    • Degradation machinery not identified in this study
  12. 2011 Medium

    Mapped β-propeller loops required for inhibition independent of syntaxin pairing and identified SUMO-2/3 conjugation at K730 as a modification that tunes inhibitory strength.

    Evidence Homology modeling, deletion mutagenesis, PC12 secretion assay, and SUMO conjugation assay

    PMID:21330375

    Open questions at the time
    • No experimental structure of the propeller
    • SUMO E3 ligase not identified here
  13. 2013 High

    Positioned tomosyn within a molecular code that dictates the timing of neurotransmitter release, inhibiting slow release in a position-dependent manner relative to UNC-13 isoforms.

    Evidence Multi-allele genetic epistasis, electrophysiology, and localization imaging in C. elegans

    PMID:23951547

    Open questions at the time
    • Molecular determinant of spatial positioning unknown
  14. 2014 High

    Demonstrated a physiological role in vascular and hemostatic exocytosis, showing STXBP5 brakes endothelial vWF/P-selectin/tPA release and platelet granule secretion via syntaxin-4 and syntaxin-11/SNAP-23.

    Evidence Co-IP, siRNA, Stxbp5 KO mice, plasma vWF/P-selectin/tPA assays, bleeding/thrombosis assays, and platelet MS/aggregometry

    PMID:24578379 PMID:25244094 PMID:25244095

    Open questions at the time
    • Why platelet KO impairs rather than enhances secretion (vs. endothelium) not fully reconciled
    • Cytoskeletal association role unresolved
  15. 2014 High

    Reconstituted full-length tomosyn inhibition of liposome fusion and resolved the spatial nanoscale organization of tomosyn–syntaxin–SNAP25 ternary complexes that mediate inhibition.

    Evidence In vitro liposome fusion with purified protein and truncations; dSTORM super-resolution with deletion mutagenesis and exocytosis assays

    PMID:24782308 PMID:25063806

    Open questions at the time
    • Relative in vivo contribution of binary vs. ternary complexes uncertain
  16. 2014 High

    Defined the phosphorylation-dependent degradation circuit for tomosyn-2, identifying HRD1 as the E3 ligase and Akt as a kinase that de-represses secretion by abrogating syntaxin-4 binding.

    Evidence 32P labeling, MS phosphosite mapping, mutagenesis, ubiquitination/proteasome assays, and GLUT4/insulin secretion readouts

    PMID:25002582 PMID:25725259

    Open questions at the time
    • Whether neuronal tomosyn-1 uses the same HRD1 pathway not shown here
  17. 2014 Medium

    Identified the SUMO E3 ligase PIASγ (PIAS4) as a direct tomosyn-1 partner mediating SUMO-2/3 modification, providing the enzymatic basis for SUMO regulation.

    Evidence Yeast two-hybrid, bidirectional co-IP in HEK293T, and SUMO modification assay

    PMID:24614299

    Open questions at the time
    • Functional consequence on secretion not tested in this study
  18. 2015 Medium

    Established tomosyn as a regulator of presynaptic plasticity and synaptic vesicle pool partitioning, acting through Cdk5 phosphorylation and Rab3A-GTP/synapsin interactions.

    Evidence KD-optogenetics in hippocampal slices with plasticity electrophysiology; VGlut1-pHluorin pool assay with co-IP and Cdk5 phosphorylation assay

    PMID:26166572 PMID:27807164

    Open questions at the time
    • Single-lab studies
    • Direct link between pool partitioning and SNARE arrest not fully defined
  19. 2016 Medium

    Showed STXBP5 is an endogenous brake on hippocampal glutamate release that opposes epileptogenesis in vivo.

    Evidence In vivo glutamate microelectrode arrays and amygdala kindling in STXBP5 KO mice

    PMID:28948088

    Open questions at the time
    • Mechanistic link to seizure circuits beyond glutamate release not established
  20. 2017 High

    Resolved the sequential SNARE-assembly pathway placing tomosyn arrest upstream of NSF/α-SNAP release, Munc18-1 scaffolding, and Munc13-1 catalysis, and genetically defined tomosyn and Munc18 as antagonists.

    Evidence In vitro reconstitution with purified NSF/α-SNAP, Munc18-1/Munc13-1; unc-18;tom-1;unc-13 genetic epistasis with electrophysiology and liposome fusion

    PMID:28821673 PMID:29485200

    Open questions at the time
    • Kinetics of in vivo handoff between tomosyn release and fusogenic assembly not quantified
  21. 2017 Medium

    Defined glucose-regulated SUMOylation at K298 and a secretagogin/Ca2+ axis as coordinated inputs that release syntaxin-1A to amplify insulin secretion.

    Evidence K298 mutagenesis, SUMO and secretagogin binding assays, and human beta-cell exocytosis measurements

    PMID:28325894

    Open questions at the time
    • Single-lab data
    • Interplay between K298 and K730 SUMO sites unresolved
  22. 2017 Medium

    Demonstrated HRD1-dependent ubiquitin-proteasomal degradation of neuronal tomosyn-1 controls its abundance and downstream dendritic spine density.

    Evidence Ubiquitin/HRD1 co-IP, in vitro ubiquitination, proteasome inhibition, and bidirectional shRNA with spine quantification in hippocampal neurons

    PMID:29269412

    Open questions at the time
    • Single-lab study
    • Signal triggering HRD1-tomosyn engagement in neurons unknown
  23. 2018 Medium

    Extended the inhibitory clamp model to immune secretion, showing PKCδ-driven phosphorylation switches tomosyn-1 between syntaxin-4 and syntaxin-3 to permit FcεRI-triggered mast cell degranulation.

    Evidence Reciprocal co-IP, phosphorylation assays, PKCδ inhibitor/knockout, degranulation assay, and patient basophil analysis

    PMID:29970602

    Open questions at the time
    • Single-lab study
    • Phosphosites mediating the syntaxin partner switch not mapped
  24. 2020 High

    Provided genetic and biochemical confirmation that tomosyn restrains GLUT4 exocytosis by inhibiting all relevant SNARE complexes, with NSF/α-SNAP relieving the arrest.

    Evidence CRISPR-Cas9 double KO in adipocytes with GLUT4 exocytosis and in vitro liposome fusion plus NSF/α-SNAP disassembly

    PMID:32851733

    Open questions at the time
    • Physiological trigger for NSF/α-SNAP-mediated tomosyn removal in adipocytes not defined
  25. 2020 Medium

    Uncovered a SNARE-independent postsynaptic function: tomosyn suppresses RhoA via its WD40 domain to maintain dendrites, spines, and surface AMPA receptors, with ASD variants causing loss of function.

    Evidence shRNA KD in primary neurons, RhoA activity assay, morphometry, AMPAR surface assays, mEPSC recordings, and domain/variant rescue

    PMID:32133675

    Open questions at the time
    • Single-lab study
    • Direct biochemical link between WD40 domain and RhoA regulators not established
  26. 2021 Medium

    Showed tomosyn sets release probability and tonic vs. phasic release identity, acting as a decoy SNARE that enables facilitation and homeostatic plasticity at tonic synapses.

    Evidence Genetic loss-of-function in Drosophila motoneurons with plasticity electrophysiology and immunofluorescence quantification

    PMID:34713802

    Open questions at the time
    • Single-lab study
    • Mechanism setting differential tomosyn expression between motoneuron types unknown
  27. 2023 High

    Revised the model for dense-core vesicles by showing tomosyns function in DCV cargo packaging/biogenesis at the Golgi—independently of the SNARE domain—rather than DCV fusion.

    Evidence Conditional double-KO mouse neurons, pHluorin single-vesicle DCV exocytosis, cargo quantification, SNARE-domain-deleted rescue, and trans-Golgi/DCV morphometry

    PMID:37695731

    Open questions at the time
    • Molecular partner mediating Golgi/cargo-packaging function unidentified
    • Reconciliation with prior invertebrate DCV-fusion data incomplete
  28. 2023 Medium

    Identified synaptotagmin-9 as an upstream partner stabilizing tomosyn-1 to enforce inhibition of insulin secretion, and reinforced TOM-1 isoform-specific roles in netrin/UNC-5-directed growth cone protrusion.

    Evidence Co-localization/co-IP, Syt9 KO/KD with tomosyn-1 rescue and SNARE/insulin assays; C. elegans tom-1;unc-5;unc-64 isoform-specific epistasis

    PMID:37014062 PMID:37432648

    Open questions at the time
    • Single-lab studies
    • How Syt9 stabilizes tomosyn-1 against proteasomal degradation unresolved
  29. 2025 Medium

    Revealed a dual role for tomosyn-2 in beta-cells, coupling inhibition of insulin granule exocytosis with promotion of beta-cell proliferation via Akt1/cell-cycle signaling.

    Evidence Co-IP, tomosyn-2 KO mice, glucose tolerance/insulin secretion assays, transcriptomics, and Akt1/cyclinD1 signaling assays

    PMID:42008692

    Open questions at the time
    • Single-lab study not independently replicated
    • Mechanistic link between tomosyn-2 and Akt1 signaling unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How tomosyn's canonical SNARE-clamp activity and its SNARE-independent functions (RhoA suppression, Golgi DCV cargo packaging) are integrated within a single protein, and what governs their tissue- and context-specific deployment, remains unresolved.
  • No structure of the full-length protein or WD40 domain
  • Partner mediating Golgi cargo-packaging function unknown
  • Determinants of context-specific t-SNARE partner choice undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140313 molecular sequestering activity 4 GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-1430728 Metabolism 5 R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-109582 Hemostasis 2 R-HSA-168256 Immune System 2
Partners
HRD1PIAS4RAB3ASNAP23SNAP25STX11STX1ASTX4
Complex memberships
tomosyn–syntaxin-11–SNAP-23 complextomosyn–syntaxin-1–SNAP-25 SNARE complextomosyn–syntaxin-4–SNAP-23 complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Tomosyn (STXBP5) was identified as a syntaxin-1-binding protein that displaces Munc18 from syntaxin-1 and forms a novel 10S complex with syntaxin-1, SNAP-25, and synaptotagmin. High-level expression of tomosyn in PC12 cells specifically reduced Ca2+-dependent exocytosis. Co-immunoprecipitation, biochemical fractionation, PC12 cell overexpression assay Neuron High 9620695
2003 The C-terminal R-SNARE motif of tomosyn forms genuine four-helical bundle SNARE core complexes with syntaxin-1 and SNAP-25, competing with synaptobrevin for binding to endogenous syntaxin/SNAP-25 on plasma membranes. Tomosyn-SNARE complexes are disassembled by NSF/α-SNAP ATPase activity. Overexpression in PC12 cells massively reduces exocytosis without altering individual fusion event parameters. In vitro reconstitution with recombinant proteins, CD spectroscopy, inside-out plasma membrane sheets competition assay, NSF disassembly assay, PC12 cell overexpression capacitance measurements The Journal of biological chemistry High 12782620
2004 Crystal structure of the tomosyn R-SNARE core complex with syntaxin-1a and SNAP-25 resolved at 2.0 Å. The complex forms a four-helical bundle highly similar to the synaptobrevin-containing SNARE complex. Synaptobrevin cannot displace the tomosyn helix from the assembled complex (and vice versa), indicating both are thermodynamic end products. Complexin binding to the tomosyn complex is impaired due to surface differences. X-ray crystallography (2.0 Å), CD spectroscopy kinetics, displacement assay The Journal of biological chemistry High 15316007
2004 Tomosyn inhibits the priming step of large dense-core vesicle exocytosis in adrenal chromaffin cells, reducing the number of fusion-competent vesicles by ~50% without affecting docked vesicle number or individual fusion kinetics. This inhibition is partially relieved at elevated calcium concentrations, indicating a calcium-dependent shift in release threshold. Capacitance measurements, amperometry, morphological analysis (electron microscopy), calcium ramp experiments in chromaffin cells Proceedings of the National Academy of Sciences of the United States of America High 14983051
2004 Tomosyn localizes at growth cone palms via binding to ROCK-phosphorylated syntaxin-1 (Rho/ROCK phosphorylates syntaxin-1, increasing its affinity for tomosyn), thereby inhibiting SNARE-mediated vesicle fusion at palm regions and promoting vesicle transport to leading edges to regulate neurite extension and retraction. Immunolocalization, co-immunoprecipitation, kinase assay (ROCK phosphorylation of syntaxin-1), neuronal overexpression/dominant-negative experiments The Journal of cell biology Medium 15240567
2005 Tomosyn is directly phosphorylated by PKA; this phosphorylation reduces its interaction with syntaxin-1, enhances SNARE complex formation, increases the readily releasable pool of synaptic vesicles, and thereby enhances neurotransmitter release. This mechanism underlies PACAP-induced facilitation of neurotransmitter release in SCG neurons. In vitro kinase assay, co-immunoprecipitation, electrophysiology in SCG neurons, pharmacological manipulation with PKA activators The Journal of cell biology High 16186257
2003 Tomosyn interacts with the t-SNAREs syntaxin-4 and SNAP-23 (adipocyte SNARE complex), forming a high-affinity ternary complex competitively inhibited by VAMP-2. The VAMP-like domain of tomosyn mediates the interaction with syntaxin-4. Overexpression of tomosyn in 3T3-L1 adipocytes inhibits insulin-stimulated GFP-GLUT4 translocation to the plasma membrane. Munc18c interacts with both syntaxin-4/tomosyn complexes and syntaxin-4-containing SNARE complexes. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation, GFP-GLUT4 translocation assay in adipocytes The Journal of biological chemistry High 12832401
2006 C. elegans TOM-1 (tomosyn ortholog) negatively regulates synaptic vesicle priming in vivo. tom-1 mutants show increased primed vesicle numbers at the plasma membrane, enhanced evoked responses, and enhanced hyperosmotic responses. Epistasis with unc-13 priming-defective mutants shows TOM-1 acts as an endogenous inhibitor of the primed vesicle pool. Electrophysiology (evoked postsynaptic currents, hyperosmotic responses), electron microscopy ultrastructure, genetic epistasis (tom-1; unc-13 double mutants), neuronal rescue expression PLoS biology High 16895441
2006 Tomosyn is expressed in pancreatic beta-cells; syntaxin-1 co-immunoprecipitates with tomosyn. Overexpression of m-tomosyn in mouse beta-cells significantly decreased exocytosis, while siRNA knockdown of tomosyn increased exocytosis, demonstrating that tomosyn negatively regulates insulin exocytosis. Co-immunoprecipitation, tomosyn overexpression in primary beta-cells, siRNA knockdown, exocytosis measurements Diabetes Medium 16505218
2006 Tomosyn-1 localizes to compartments enriched in insulin granules in beta-cells. The SNARE-like domain of tomosyn-1 forms a complex with syntaxin-1 and SNAP25 with weaker binding forces than VAMP2 (237 vs. 279 pN by AFM). siRNA silencing of tomosyn-1 reduces stimulus-induced exocytosis without affecting the number of docked granules, indicating tomosyn-1 facilitates a post-docking event required for exocytosis. Atomic force microscopy binding force measurements, siRNA knockdown, electron microscopy (docked granule counting), stimulus-secretion assay Journal of cell science Medium 16787939
2007 C. elegans TOM-1 negatively regulates dense-core vesicle (DCV) exocytosis. tom-1 mutants show 50% reduction in presynaptic DCVs corresponding to enhanced neuropeptide release; TOM-1 overexpression causes DCV accumulation. Genetic epistasis shows TOM-1 antagonizes UNC-31 (CAPS)-dependent DCV release; loss of TOM-1 suppresses unc-31 behavioral, electrophysiological, and ultrastructural phenotypes. Electron microscopy ultrastructure, electrophysiology, genetic epistasis (tom-1;unc-31 double mutants), neuropeptide release assays, behavioral analysis The Journal of neuroscience High 17881523
2007 The N-terminal WD40 repeat domain of tomosyn is required for its inhibitory activity and is sufficient to inhibit neurotransmitter release by catalyzing oligomerization of SNARE complexes. The C-terminal VAMP-like domain (VLD) inhibits SNARE complex formation by sequestering syntaxin-1. Together, these represent a dual inhibitory mechanism. Microinjection of the isolated N-terminal WD40 domain into neurons prevented stimulated acetylcholine release. Microinjection of domain-truncation constructs into neurons, co-immunoprecipitation to assess SNARE complex oligomerization, tomosyn-KO mouse analysis The Journal of cell biology High 18936251
2007 Secretagogue stimulation causes rapid translocation of tomosyn from cytosol to plasma membrane regions in chromaffin cells, associated with increased tomosyn–syntaxin-1A interaction and increased cycling of tomosyn into SNARE complexes. This translocation is strongly reduced by ROCK inhibition, consistent with RhoA-mediated regulation. LPA (a RhoA activator) mimics secretagogue-induced tomosyn–syntaxin interaction. Live-cell optical imaging (FRET/translocation assay), pharmacological ROCK inhibition, LPA stimulation, co-immunoprecipitation, PC12 secretory assays The Journal of biological chemistry Medium 17545156
2007 Tomosyn's inhibition of exocytosis requires the integrity of its N-terminal WD40 domain; a tomosyn mutant lacking the entire SNARE domain inhibits vesicle priming as potently as full-length protein, while the isolated SNARE domain fails to inhibit exocytosis. An N-terminally truncated mutant that retains SNARE-domain syntaxin binding does not inhibit exocytosis. Both the WD40 repeats and linker are required for inhibitory function. Domain-deletion mutant overexpression in chromaffin cells, capacitance measurements, co-immunoprecipitation Journal of neurochemistry Medium 17666050
2011 Positional cloning and functional characterization identified tomosyn-2 (STXBP5L) as a negative regulator of insulin secretion. Tomosyn-2 binds syntaxin-1A and syntaxin-4 in vitro; overexpression in INS1 cells inhibits insulin secretion. The BTBR allele of tomosyn-2 resists proteasomal degradation compared to the B6 allele, establishing a functional consequence of a coding SNP. In vitro binding assay with recombinant proteins, INS1 cell overexpression secretion assay, proteasomal degradation assay, sub-congenic mouse islet secretion phenotyping PLoS genetics High 21998599
2011 Structural analysis by homology modeling (based on yeast Sro7 crystal structure) reveals that deletion of loops 1 and 3 from the β-propeller core of tomosyn eliminates its inhibitory activity on secretion without altering SNARE pairing with syntaxin-1A. Deletion of loop 2 (hypervariable splice region) does not reduce inhibition but affects protein accumulation of tomosyn-2 isoforms. m-Tomosyn-1 is a substrate for SUMO-2/3 conjugation at K730; mutation of this site enhances secretion inhibition without altering syntaxin-1A binding. Homology modeling, deletion mutagenesis, PC12 cell secretion assay, co-immunoprecipitation, SUMO conjugation assay The Journal of biological chemistry Medium 21330375
2013 In C. elegans, Tomosyn inhibits slow neurotransmitter release while UNC-13L mediates fast release. Tomosyn's spatial position (diffuse/distal from dense projection) correlates with its control over slow release. Genetic analysis places tomosyn as a negative regulator in a molecular code (UNC-13L, UNC-13S, and Tomosyn) that dictates the timing of neurotransmitter release. Genetic epistasis (multiple mutant combinations), electrophysiology, fluorescence imaging of protein localization eLife High 23951547
2014 STXBP5 is expressed in human endothelial cells and colocalizes with and binds syntaxin-4. Knockdown of STXBP5 in endothelial cells increases exocytosis of vWF and P-selectin. Stxbp5 KO mice have higher plasma vWF, increased P-selectin translocation, and more platelet-endothelial interactions, demonstrating that STXBP5 inhibits endothelial exocytosis. Stxbp5 KO mice also have defects in platelet secretion and hemostasis (prolonged bleeding times, impaired thrombosis). Co-immunoprecipitation, siRNA knockdown (endothelial cells), Stxbp5 KO mouse model, plasma vWF ELISA, P-selectin translocation FACS, tail bleeding and mesenteric/carotid thrombosis assays The Journal of clinical investigation High 25244095
2014 STXBP5 was identified by mass spectrometry from SNARE-containing affinity purifications from human platelet extracts. STXBP5 interacts with syntaxin-11/SNAP23 heterodimers by co-immunoprecipitation and also associates with the platelet cytoskeleton. Stxbp5 KO platelets have markedly defective stimulation-dependent secretion from all three granule types (dense, alpha, lysosomal) and altered granule cargo levels despite normal granule numbers and morphology. Mass spectrometry, co-immunoprecipitation, fractionation, Stxbp5 KO mouse model, lumi-aggregometry, FACS (P-selectin/LAMP-1), bone marrow transplantation The Journal of clinical investigation High 25244094
2014 The C-terminal domain (CTD) of tomosyn, containing the R-SNARE-like motif, mediates inhibition of SNARE-dependent membrane fusion by recognizing the t-SNARE complex and preventing pairing with the v-SNARE, arresting the fusion reaction at a pre-docking stage. The N-terminal domain (NTD) is critical (but not sufficient) for tomosyn recruitment to fusion sites via syntaxin monomer binding. Tomosyn inhibitory activity is dominant over the stimulatory Sec1/Munc18 protein in fusion. In vitro reconstituted SNARE-dependent liposome fusion assay with purified full-length tomosyn and domain truncations, co-immunoprecipitation The Journal of biological chemistry High 25063806
2014 In vitro, tomosyn-2 is phosphorylated in response to glucose, phorbol esters, and cAMP analogs; 11 phosphorylation sites were identified by mass spectrometry. Phosphomimetic (Ser→Asp) tomosyn-2 shows enhanced proteasomal turnover and reduced ability to inhibit insulin secretion. Tomosyn-2 is ubiquitinated by the E3 ligase Hrd-1; Hrd-1 knockdown increases tomosyn-2 abundance, identifying a phosphorylation-dependent proteasomal degradation mechanism for de-repression of insulin secretion. 32P labeling, mass spectrometry phosphosite identification, site-directed mutagenesis, proteasome inhibitor experiments, proteomic screen for binding partners, co-immunoprecipitation, shRNA knockdown, ubiquitination assay The Journal of biological chemistry High 25002582
2014 By dSTORM super-resolution imaging, tomosyn is organized in small clusters adjacent to syntaxin clusters on the plasma membrane. Tomosyn forms both binary (tomosyn–syntaxin) and ternary (tomosyn–syntaxin–SNAP25) complexes at the PM. Deletion of β-propeller core residues 537–578 or 897–917 reduces SNAP25 binding and PM cluster residence time, shifting equilibrium toward binary tomosyn–syntaxin complexes and reducing inhibition of exocytosis, indicating tomosyn inhibits exocytosis via the ternary complex. dSTORM super-resolution microscopy, deletion mutagenesis, co-immunoprecipitation, fluorescence recovery assays, exocytosis assay The Journal of biological chemistry Medium 24782308
2014 STXBP5 knockdown in vascular endothelial cells decreased tPA release, functionally linking STXBP5 to regulation of tPA exocytosis from endothelium. siRNA knockdown in vascular endothelial cells, tPA release assay Arteriosclerosis, thrombosis, and vascular biology Medium 24578379
2015 Tomosyn is phosphorylated at Ser-783 by both Akt1 and Akt2; this phosphorylation inhibits tomosyn's interaction with syntaxin-4, as shown by in vitro pull-down. Expression of phosphorylation-deficient (S783A) tomosyn attenuates insulin-stimulated GLUT4 surface expression, suggesting that Akt-mediated phosphorylation of tomosyn relieves its inhibition of GLUT4 exocytosis. In vitro kinase assay (Akt1/Akt2), in vitro pulldown assay, intact cell 32P labeling with PI3K inhibitor, GLUT4 cell-surface assay with mutant overexpression The international journal of biochemistry & cell biology Medium 25725259
2015 Tomosyn knockdown at hippocampal mossy fiber–CA3 synapses (via combined lentiviral KD and optogenetic activation) impairs synaptic facilitation, PKA-dependent long-term potentiation, and PKA-induced potentiation. This establishes tomosyn as a key regulator of mossy fiber presynaptic plasticity. Combined KD-optogenetic strategy in hippocampal slices, electrophysiology (facilitation, LTP, PKA-induced potentiation) Cell reports Medium 26166572
2016 Tomo1 regulates synaptic vesicle pool partitioning at rat hippocampal synapses in an activity-dependent manner. Tomo1 knockdown facilitates release from the Readily Releasable Pool (RRP) and alters Total Recycling Pool and Resting Pool distribution. These effects are regulated by Cdk5-dependent phosphorylation of Tomo1. Tomo1 interacts with GTP-bound Rab3A and, via Rab3A, with Synapsin 1a/b. VGlut1-pHluorin fluorescence SV pool assay, KD and rescue, co-immunoprecipitation (Tomo1–Rab3A-GTP, Tomo1–Synapsin), Cdk5 phosphorylation assay, chronic activity manipulation The Journal of neuroscience Medium 27807164
2017 Tomosyn negatively regulates SNARE complex formation in a manner requiring its SUMOylation at K298. Glucose-dependent de-SUMOylation of tomosyn-1 releases syntaxin-1A. Tomosyn-1 interacts with secretagogin, a Ca2+-binding protein that dissociates from tomosyn-1 in response to Ca2+-raising stimuli and is required for insulin granule trafficking and exocytosis. Together, SUMOylation and Ca2+-dependent secretagogin release coordinate amplification of insulin secretion. Co-immunoprecipitation, site-directed mutagenesis (K298), SUMO modification assay, secretagogin binding assay, human beta-cell exocytosis measurements Scientific reports Medium 28325894
2017 UNC-18(P334A) gain-of-function in C. elegans partially bypasses UNC-13 requirement for synaptic vesicle fusion and shows synergistic suppression with tom-1 null mutation, placing tomosyn/TOM-1 and Munc18/UNC-18 as antagonistic regulators of SNARE complex assembly downstream of Munc13/UNC-13. Biochemically, Munc18-1(P335A) shows enhanced SNARE complex formation and partial bypass of Munc13-1 requirement in liposome fusion assays. Genetic epistasis (unc-18; tom-1; unc-13 multiple mutants), electrophysiology, liposome fusion assay, co-immunoprecipitation (SNARE complex formation) The Journal of neuroscience High 28821673
2017 Tomosyn-1 is ubiquitinated in hippocampal neurons and undergoes HRD1-dependent proteasomal degradation. Immunoprecipitation of Tomo-1 from neurons co-precipitates HRD1, and in vitro reactions show direct, HRD1 concentration-dependent Tomo-1 ubiquitination. HRD1 knockdown increases Tomo-1 levels and dendritic spine density; Tomo-1 co-knockdown reverses this effect, establishing a direct HRD1→Tomo-1 effector relationship. Immunoprecipitation (ubiquitin/HRD1), in vitro ubiquitination assay, proteasome inhibitor treatment, shRNA KD (HRD1 and Tomo-1), dendritic spine density quantification The Journal of biological chemistry Medium 29269412
2018 Tomosyn-1 (STXBP5) acts as an inhibitory fusion clamp in mast cell degranulation downstream of FcεRI. After activation, tomosyn-1 is phosphorylated on serine and threonine residues, dissociates from syntaxin-4 (STX4), and re-associates with syntaxin-3 (STX3). PKCδ is the major kinase required for tomosyn-1 threonine phosphorylation and for regulating the switch between STX partners. Co-immunoprecipitation (tomosyn-STX4/STX3 interactions), phosphorylation assays, PKCδ inhibitor/knockout studies, FcεRI-stimulated degranulation assay, patient basophil analysis Science signaling Medium 29970602
2018 NSF/α-SNAP disassembles the tomosyn-SNARE arrest complex, allowing syntaxin-1 to enter the Munc18-1/syntaxin-1 complex. Munc13-1 then catalyzes transfer of syntaxin-1 from the Munc18-1/syntaxin-1 complex into the SNARE complex in a manner specific to synaptobrevin-2 but resistant to tomosyn. This establishes a sequential pathway: tomosyn arrest → NSF/α-SNAP release → Munc18-1 scaffolding → Munc13-1 SNARE assembly. In vitro biochemical reconstitution with purified proteins (NSF/α-SNAP disassembly assay, Munc18-1/Munc13-1 SNARE assembly assay), co-immunoprecipitation FEBS letters High 29485200
2020 CRISPR-Cas9 double knockout of both tomosyn-encoding genes in adipocytes markedly elevated both basal and insulin-stimulated GLUT4 exocytosis without affecting adipocyte differentiation or insulin signaling. In reconstituted liposome fusion, tomosyn inhibited all SNARE complexes underlying GLUT4 exocytosis, and this inhibition was relieved by NSF/α-SNAP, which removes tomosyn from GLUT4 exocytic SNAREs. CRISPR-Cas9 double KO in adipocytes, GLUT4 exocytosis assay, in vitro liposome fusion reconstitution with purified tomosyn, NSF/α-SNAP disassembly assay Traffic High 32851733
2020 Tomosyn knockdown in mouse primary neurons increases RhoA GTPase activity, leading to compromised dendritic arborization, loss of dendritic spines, decreased surface AMPA receptor expression, and reduced mEPSC frequency. Inhibiting RhoA signaling rescues the morphological and receptor surface expression defects. The N-terminal WD40 domain mediates tomosyn's suppression of RhoA activity. Two ASD-associated missense variants in the WD40 domain show loss-of-function for these postsynaptic phenotypes. shRNA knockdown in primary neurons, RhoA GTPase activity assay, dendritic spine/arborization morphometry, AMPA receptor surface expression (immunostaining/biotinylation), mEPSC recordings, domain truncation and ASD variant rescue experiments Journal of neuroscience research Medium 32133675
2021 In Drosophila, Tomosyn acts as a decoy SNARE that sets release probability (Pr) and tonic vs. phasic release properties. Tomosyn is differentially expressed between tonic (Ib, high Tomosyn, low Pr) and phasic (Is, low Tomosyn, high Pr) motoneurons. Loss of Tomosyn impairs synaptic facilitation, LTP, and presynaptic homeostatic potentiation specifically at tonic synapses. Genetic loss-of-function in Drosophila motoneurons, electrophysiology (evoked responses, facilitation, homeostatic plasticity), immunofluorescence protein quantification eLife Medium 34713802
2023 In tomosyn/tomosyn-2 conditional double-knockout mouse neurons, DCV exocytosis frequency was not significantly affected; however, intracellular levels of DCV cargos (NPY, BDNF) were strongly reduced. BDNF levels were restored by re-expression of tomosyn but not by lysosomal protease inhibition, and tomosyn's SNARE domain was dispensable for rescue. Trans-Golgi network and DCV size were decreased, and DCV cargo flux through Golgi was accelerated in KO neurons, suggesting tomosyns function in DCV biogenesis/cargo packaging at the Golgi rather than DCV fusion. Conditional double-KO mouse neurons, pHluorin-based single-vesicle DCV exocytosis assay, cargo level quantification (NPY, BDNF), tomosyn re-expression rescue (full-length and SNARE-domain-deleted), trans-Golgi network morphometry, DCV size analysis eLife High 37695731
2023 C. elegans TOM-1 short isoform acts downstream of the UNC-5 netrin receptor to inhibit growth cone protrusion, and this mechanism requires syntaxin/UNC-64, consistent with TOM-1 inhibiting vesicle fusion needed for membrane addition during protrusion. The long TOM-1 isoform has a pro-protrusive role. Genetic epistasis in C. elegans (tom-1; unc-5; unc-64 mutant analysis), growth cone protrusion quantification, isoform-specific rescue experiments Development Medium 37014062
2014 Tomosyn-1 interacts with the SUMO E3 ligase PIASγ (PIAS4). The interaction involves the C-terminus of tomosyn-1 and the N-terminus of PIASγ, confirmed by yeast two-hybrid and bidirectional immunoprecipitation in HEK293T cells. Tomosyn-1 is preferentially modified by SUMO-2/3. Yeast two-hybrid, bidirectional co-immunoprecipitation in HEK293T cells, SUMO modification assay PloS one Medium 24614299
2023 Synaptotagmin-9 (Syt9) colocalizes and binds tomosyn-1 and syntaxin-1A (Stx1A) in pancreatic beta-cells; the Syt9–tomosyn-1–Stx1A complex is inhibitory for insulin secretion. Syt9 knockdown reduces tomosyn-1 protein abundance via proteasomal degradation, decreases tomosyn-1/Stx1A interaction, and increases SNARE complex formation and insulin secretion. Rescuing tomosyn-1 blocks the Syt9-knockdown-mediated increases in insulin secretion, establishing that Syt9's inhibitory effects on insulin secretion are mediated through tomosyn-1. Co-localization, co-immunoprecipitation, Syt9 KO/KD (mouse and cell), tomosyn-1 rescue expression, SNARE complex assay, insulin secretion assay FASEB journal Medium 37432648
2016 STXBP5/tomosyn-1 KO mice show increased KCl-evoked glutamate release in the hippocampal dentate gyrus and accelerated kindling progression (fewer stimuli required to reach fully kindled state), establishing STXBP5 as an endogenous brake on glutamate release that opposes epileptiform activity. Glutamate-selective microelectrode array (MEA) in vivo measurements, amygdala kindling stimulation, STXBP5 KO mouse model Brain and behavior Medium 28948088
2025 Tomosyn-2 interacts with syntaxin-1A to inhibit insulin granule exocytosis by limiting SNARE complex formation in pancreatic beta-cells. Tomosyn-2 KO mice show improved glucose clearance and enhanced biphasic insulin secretion. Loss of tomosyn-2 also reduces beta-cell proliferation via downregulation of Akt1 signaling and cell-cycle mediators, identifying a dual role in insulin secretion and beta-cell maturation. Co-immunoprecipitation (tomosyn-2/Stx1A), tomosyn-2 KO mouse model, glucose tolerance tests, insulin secretion assay from isolated islets, transcriptomic analysis, Akt1/cyclinD1 signaling assay Diabetes Medium 42008692

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process. Neuron 240 9620695
1999 Yeast homologues of tomosyn and lethal giant larvae function in exocytosis and are associated with the plasma membrane SNARE, Sec9. The Journal of cell biology 184 10402465
2006 Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans. PLoS biology 130 16895441
2003 The R-SNARE motif of tomosyn forms SNARE core complexes with syntaxin 1 and SNAP-25 and down-regulates exocytosis. The Journal of biological chemistry 108 12782620
2004 Tomosyn inhibits priming of large dense-core vesicles in a calcium-dependent manner. Proceedings of the National Academy of Sciences of the United States of America 85 14983051
2005 PKA-catalyzed phosphorylation of tomosyn and its implication in Ca2+-dependent exocytosis of neurotransmitter. The Journal of cell biology 83 16186257
2004 Structural basis for the inhibitory role of tomosyn in exocytosis. The Journal of biological chemistry 80 15316007
2013 UNC-13L, UNC-13S, and Tomosyn form a protein code for fast and slow neurotransmitter release in Caenorhabditis elegans. eLife 76 23951547
2003 Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation. The Journal of biological chemistry 73 12832401
2014 Syntaxin-binding protein STXBP5 inhibits endothelial exocytosis and promotes platelet secretion. The Journal of clinical investigation 69 25244095
2008 Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release. The Journal of cell biology 65 18936251
2011 Positional cloning of a type 2 diabetes quantitative trait locus; tomosyn-2, a negative regulator of insulin secretion. PLoS genetics 64 21998599
2004 Regulation of SNAREs by tomosyn and ROCK: implication in extension and retraction of neurites. The Journal of cell biology 64 15240567
2006 Tomosyn is expressed in beta-cells and negatively regulates insulin exocytosis. Diabetes 53 16505218
2019 LncRNA STXBP5-AS1 suppressed cervical cancer progression via targeting miR-96-5p/PTEN axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 52 31212131
2015 CLEC4M and STXBP5 gene variations contribute to von Willebrand factor level variation in von Willebrand disease. Journal of thrombosis and haemostasis : JTH 52 25832887
2007 Tomosyn negatively regulates CAPS-dependent peptide release at Caenorhabditis elegans synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 17881523
2014 Platelet secretion and hemostasis require syntaxin-binding protein STXBP5. The Journal of clinical investigation 46 25244094
2006 Tomosyn-1 is involved in a post-docking event required for pancreatic beta-cell exocytosis. Journal of cell science 46 16787939
2009 Friends and foes in synaptic transmission: the role of tomosyn in vesicle priming. Trends in neurosciences 43 19307030
2005 Two distinct genes drive expression of seven tomosyn isoforms in the mammalian brain, sharing a conserved structure with a unique variable domain. Journal of neurochemistry 41 15659226
2011 Structural and functional analysis of tomosyn identifies domains important in exocytotic regulation. The Journal of biological chemistry 40 21330375
2005 Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion. PLoS genetics 38 16103915
2014 Genome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2. Arteriosclerosis, thrombosis, and vascular biology 37 24578379
2007 Multiple functional domains are involved in tomosyn regulation of exocytosis. Journal of neurochemistry 36 17666050
2017 SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells. Scientific reports 35 28325894
2007 Receptor-mediated regulation of tomosyn-syntaxin 1A interactions in bovine adrenal chromaffin cells. The Journal of biological chemistry 34 17545156
1999 Three splicing variants of tomosyn and identification of their syntaxin-binding region. Biochemical and biophysical research communications 34 10066450
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
2007 Tomosyn negatively regulates both synaptic transmitter and neuropeptide release at the C. elegans neuromuscular junction. The Journal of physiology 31 17627987
2011 Tomosyn-dependent regulation of synaptic transmission is required for a late phase of associative odor memory. Proceedings of the National Academy of Sciences of the United States of America 30 22042858
2019 Long noncoding RNA STXBP5-AS1 inhibits cell proliferation, migration, and invasion through inhibiting the PI3K/AKT signaling pathway in gastric cancer cells. OncoTargets and therapy 27 30881044
2016 Dynamic Partitioning of Synaptic Vesicle Pools by the SNARE-Binding Protein Tomosyn. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 27807164
2014 Differential interaction of tomosyn with syntaxin and SNAP25 depends on domains in the WD40 β-propeller core and determines its inhibitory activity. The Journal of biological chemistry 27 24782308
2015 A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity. Cell reports 25 26166572
2014 The N- and C-terminal domains of tomosyn play distinct roles in soluble N-ethylmaleimide-sensitive factor attachment protein receptor binding and fusion regulation. The Journal of biological chemistry 24 25063806
2016 Novel Thrombotic Function of a Human SNP in STXBP5 Revealed by CRISPR/Cas9 Gene Editing in Mice. Arteriosclerosis, thrombosis, and vascular biology 23 28062498
2014 Phosphorylation and degradation of tomosyn-2 de-represses insulin secretion. The Journal of biological chemistry 23 25002582
2010 Tomosyn expression pattern in the mouse hippocampus suggests both presynaptic and postsynaptic functions. Frontiers in neuroanatomy 23 21191478
2021 Ginsenoside Rh2 upregulates long noncoding RNA STXBP5-AS1 to sponge microRNA-4425 in suppressing breast cancer cell proliferation. Journal of ginseng research 22 34764730
2019 Ginsenoside Rg3 and Korean Red Ginseng extract epigenetically regulate the tumor-related long noncoding RNAs RFX3-AS1 and STXBP5-AS1. Journal of ginseng research 22 31700260
2014 Tomosyn-2 is required for normal motor performance in mice and sustains neurotransmission at motor endplates. Brain structure & function 21 24744148
2021 The decoy SNARE Tomosyn sets tonic versus phasic release properties and is required for homeostatic synaptic plasticity. eLife 20 34713802
2019 Overexpressed Tomosyn Binds Syntaxins and Blocks Secretion during Pollen Development. Plant physiology 16 31530628
2018 Tomosyn guides SNARE complex formation in coordination with Munc18 and Munc13. FEBS letters 16 29485200
2018 Tomosyn functions as a PKCδ-regulated fusion clamp in mast cell degranulation. Science signaling 16 29970602
2018 Long noncoding RNA STXBP5-AS1 inhibits cell proliferation, migration, and invasion via preventing the PI3K/AKT against STXBP5 expression in non-small-cell lung carcinoma. Journal of cellular biochemistry 15 30450569
2020 Tomosyn regulates the small RhoA GTPase to control the dendritic stability of neurons and the surface expression of AMPA receptors. Journal of neuroscience research 14 32133675
2015 Tomosyn is a novel Akt substrate mediating insulin-dependent GLUT4 exocytosis. The international journal of biochemistry & cell biology 14 25725259
2020 Genetic evidence for an inhibitory role of tomosyn in insulin-stimulated GLUT4 exocytosis. Traffic (Copenhagen, Denmark) 13 32851733
2011 In vivo analysis of conserved C. elegans tomosyn domains. PloS one 13 22022557
2017 Tomosyn associates with secretory vesicles in neurons through its N- and C-terminal domains. PloS one 12 28746398
2014 In vitro reconstitution of Rab GTPase-dependent vesicle clustering by the yeast lethal giant larvae/tomosyn homolog, Sro7. The Journal of biological chemistry 12 25404740
2021 Aberrant hypermethylation induced downregulation of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 correlate with tumorigenesis of glioma. Life sciences 10 33965377
2018 The tomosyn homologue, Sro7, is a direct effector of the Rab GTPase, Sec4, in post-Golgi vesicle tethering. Molecular biology of the cell 10 29668350
2017 Linking kindling to increased glutamate release in the dentate gyrus of the hippocampus through the STXBP5/tomosyn-1 gene. Brain and behavior 10 28948088
2017 The ubiquitin-proteasome system functionally links neuronal Tomosyn-1 to dendritic morphology. The Journal of biological chemistry 10 29269412
2015 Structural basis for recognition of the Sec4 Rab GTPase by its effector, the Lgl/tomosyn homologue, Sro7. Molecular biology of the cell 10 26202462
2014 Tomosyn interacts with the SUMO E3 ligase PIASγ. PloS one 10 24614299
2018 Genetic Variation in the Syntaxin-Binding Protein STXBP5 in Type 1 von Willebrand Disease Patients. Thrombosis and haemostasis 8 29972863
2023 Tomosyn affects dense core vesicle composition but not exocytosis in mammalian neurons. eLife 7 37695731
2003 WD-40 repeat containing rat lethal giant larvae recessive oncogene, but not m-tomosyn, restores the salt sensitivity in Saccharomyces cerevisiae. International journal of oncology 7 12792798
2019 A Potential Role for the STXBP5-AS1 Gene in Adult ADHD Symptoms. Behavior genetics 5 30659475
2023 TOM-1/tomosyn acts with the UNC-6/netrin receptor UNC-5 to inhibit growth cone protrusion in Caenorhabditis elegans. Development (Cambridge, England) 4 37014062
2016 Tomosyn Negatively Regulates Arginine Vasopressin Secretion in Embryonic Stem Cell-Derived Neurons. PloS one 4 27732637
2024 The syntaxin-binding protein STXBP5 regulates progerin expression. Scientific reports 3 39379476
2023 Genetic ablation of synaptotagmin-9 alters tomosyn-1 function to increase insulin secretion from pancreatic β-cells improving glucose clearance. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 3 37432648
2017 RESISTIN INHIBITS GLUCOSE-STIMULATED INSULIN SECRETION THROUGH MIR-494 BY TARGET ON STXBP5. Acta endocrinologica (Bucharest, Romania : 2005) 2 31149145
2026 Tomosyn-2 Regulates Postnatal β-Cell Expansion and Insulin Secretion to Maintain Glucose Homeostasis. Diabetes 0 42008692
2025 Tomosyn-2 Regulates Postnatal β-Cell Expansion and Insulin Secretion to Maintain Glucose Homeostasis. bioRxiv : the preprint server for biology 0 40475581
2023 The Role of Tomosyn in the Regulation of Neurotransmitter Release. Advances in neurobiology 0 37615869

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