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Cited by 294Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

Conformational switch of syntaxin-1 controls synaptic vesicle fusion

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Gerber, Stefan H., Rah, Jong-Cheol, Min, Sang-Won, Liu, Xinran, de Wit, Heidi, Dulubova, Irina, Meyer, Alexander C., Rizo, Josep +5 more·2008·Science
DOI 10.1126/science.1163174PMC PMC3235364
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Abstract

During synaptic vesicle fusion, the soluble N -ethylmaleimide-sensitive factor–attachment protein receptor (SNARE) protein syntaxin-1 exhibits two conformations that both bind to Munc18-1: a “closed” conformation outside the SNARE complex and an “open” conformation in the SNARE complex. Although SNARE complexes containing open syntaxin-1 and Munc18-1 are essential for exocytosis, the function of closed syntaxin-1 is unknown. We generated knockin/knockout mice that expressed only open syntaxin-1B. Syntaxin-1B Open mice were viable but succumbed to generalized seizures at 2 to 3 months of age. Binding of Munc18-1 to syntaxin-1 was impaired in syntaxin-1B Open synapses, and the size of the readily releasable vesicle pool was decreased; however, the rate of synaptic vesicle fusion was dramatically enhanced. Thus, the closed conformation of syntaxin-1 gates the initiation of the synaptic vesicle fusion reaction, which is then mediated by SNARE-complex/Munc18-1 assemblies.

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Crossref · 10.1126/science.1163174

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  • The MUN domain may act to open the 'closed' form of the SNARE protein syntaxin-1, thereby enabling syntaxin-1 to form SNARE complexes.

    “The MUN domain may act to open the ‘closed’ form of the SNARE protein syntaxin-1 (Gerber et al., 2008), thereby enabling syntaxin-1 to form SNARE complexes (Richmond et al., 2001; Ma et al., 2011).”

    From The Presynaptic Active Zone (2012) · cites this paper as Gerber et al., 2008

    The paper’s Abstract describes closed and open conformations of syntaxin-1 and reports that opening syntaxin-1 affects synaptic vesicle fusion. It does not mention the MUN domain or suggest that the domain opens syntaxin-1 (searched: “MUN domain” and “Munc13 promotes opening syntaxin-1”). The SNARE-complex clause is cited separately to other papers. (LLM, conf=0.82)

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Research works printed but not linked: 22

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Authors
Gerber, S. H., Rah, J.-C., Min, S.-W., Liu, X., de Wit, H., Dulubova, I., Meyer, A. C., Rizo, J., Arancillo, M., Hammer, R. E., Verhage, M., Rosenmund, C., & Südhof, T. C.
Affiliations
  • Baylor College of Medicine (US)
  • Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390–9111, USA.
Corresponding author
  • Gerber, Stefan H.
  • Rah, Jong-Cheol
  • Min, Sang-Won
  • Rosenmund, Christian
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2008-09-12
Volume
321
Issue
5895
Pages
1507-1510
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.1163174
PMC
PMC3235364
OpenAlex
W2006897184
Cited by
294
References
23
Citations by year
2026: 4 · 2025: 6 · 2024: 7 · 2023: 15 · 2022: 9 · 2021: 13 · 2020: 16 · 2019: 12 · 2018: 15 · 2017: 15 · 2016: 15 · 2015: 18 · 2014: 28 · 2013: 22 · 2012: 24
FWCI
10.95
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • VU Research Portal (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Neurological Disorders and Stroke (NS 37200, R01NS037200, R01NS051262, NS051262)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
syntaxin-1, Munc18-1, SNARE complex, synaptic vesicle fusion, conformational switching, exocytosis, seizures, synaptic transmission
MeSH terms
Animals, Calcium, Epilepsy, Membrane Fusion, Mutation, Protein Conformation, Sucrose, Synapses, Synaptic Vesicles, Protein Structure, Tertiary, Mice, Knockout, Excitatory Postsynaptic Potentials, SNARE Proteins, Syntaxin 1, Mice, Munc18 Proteins

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