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Cited by 114Cellular transport and secretionNeuroscience and Neuropharmacology ResearchLipid Membrane Structure and Behavior

Lipid-Anchored SNAREs Lacking Transmembrane Regions Fully Support Membrane Fusion during Neurotransmitter Release

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Zhou, Peng, Bacaj, Taulant, Yang, Xiaofei, Pang, Zhiping P., Südhof, Thomas C.·2013·Neuron
DOI 10.1016/j.neuron.2013.09.010PMC PMC3872166
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Abstract

Synaptic vesicle fusion during neurotransmitter release is mediated by assembly of SNARE- and SM-protein complexes composed of syntaxin-1, SNAP-25, synaptobrevin-2/VAMP2, and Munc18-1. Current models suggest that SNARE-complex assembly catalyzes membrane fusion by pulling the transmembrane regions (TMRs) of SNARE proteins together, thus allowing their TMRs to form a fusion pore. These models are consistent with the requirement for TMRs in viral fusion proteins. However, the role of the SNARE TMRs in synaptic vesicle fusion has not yet been tested physiologically. Here, we examined whether synaptic SNAREs require TMRs for catalysis of synaptic vesicle fusion, which was monitored electrophysiologically at millisecond time resolution. Surprisingly, we find that both lipid-anchored syntaxin-1 and lipid-anchored synaptobrevin-2 lacking TMRs efficiently promoted spontaneous and Ca(2+)-triggered membrane fusion. Our data suggest that SNARE proteins function during fusion primarily as force generators, consistent with the notion that forcing lipid membranes close together suffices to induce membrane fusion.

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  • The palmitoylated cysteine residues of SNAP-25 would be able to interact with the plasma membrane, and the membrane-proximal side of syntaxin is closely juxtaposed with the membrane, as inferred by the requirement of tight membrane-coupling of syntaxin for evoked release.

    “The palmitoylated cysteine residues of SNAP-25 would be able to interact with the plasma membrane, and the membrane-proximal side of syntaxin is closely juxtaposed with the membrane, as inferred by the requirement of tight membrane-coupling of syntaxin for evoked release47.”

    From Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis (2015) · cites this paper as [47]

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Cited by

Sorted by citations

Authors
Zhou, P., Bacaj, T., Yang, X., Pang, Z. P., & Südhof, T. C.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Südhof, Thomas C.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2013-10
Volume
80
Issue
2
Pages
470-483
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2013.09.010
PMC
PMC3872166
OpenAlex
W2060821973
Cited by
114
References
1
Citations by year
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FWCI
8.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Mental Health (R01MH089054, P50MH086403)
  • National Institute of Neurological Disorders and Stroke (R01NS077906, F32NS067896)
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 › Lipid Membrane Structure and Behavior
Keywords
SNARE proteins, membrane fusion, synaptic vesicle fusion, neurotransmitter release, syntaxin-1, synaptobrevin 2, VAMP2, transmembrane domain, fusion pore, Munc18-1, SNAP-25, force generation
MeSH terms
Animals, Cells, Cultured, Membrane Fusion, Membrane Lipids, Mice, Transgenic, Synaptic Transmission, Neurons, Synaptic Vesicles, Mice, Knockout, Neurotransmitter Agents, SNARE Proteins, Syntaxin 1, Vesicle-Associated Membrane Protein 2, Mice, Inhibitory Postsynaptic Potentials

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