Cited by 2,027Cellular transport and secretionLipid Membrane Structure and BehaviorExtracellular vesicles in disease

Membrane Fusion: Grappling with SNARE and SM Proteins

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Südhof, Thomas C., Rothman, James E.·2009·Science

Abstract

The two universally required components of the intracellular membrane fusion machinery, SNARE and SM (Sec1/Munc18-like) proteins, play complementary roles in fusion. Vesicular and target membrane–localized SNARE proteins zipper up into an α-helical bundle that pulls the two membranes tightly together to exert the force required for fusion. SM proteins, shaped like clasps, bind to trans-SNARE complexes to direct their fusogenic action. Individual fusion reactions are executed by distinct combinations of SNARE and SM proteins to ensure specificity, and are controlled by regulators that embed the SM-SNARE fusion machinery into a physiological context. This regulation is spectacularly apparent in the exquisite speed and precision of synaptic exocytosis, where synaptotagmin (the calcium-ion sensor for fusion) cooperates with complexin (the clamp activator) to control the precisely timed release of neurotransmitters that initiates synaptic transmission and underlies brain function.

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Crossref · 10.1126/science.1161748

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  • Plasma membrane SNARE proteins syntaxin and SNAP-25 and the SM protein Munc18 are not enriched in active zones but distributed all over the plasma membrane.

    “Furthermore, as noted above, the plasma membrane SNARE proteins syntaxin and SNAP-25 and the SM protein Munc18 that are components of the synaptic vesicle fusion machinery for exocytosis (Südhof and Rothman, 2009) are not enriched in active zones but distributed all over the plasma membrane.”

    From The Presynaptic Active Zone (2012) · cites this paper as Südhof and Rothman, 2009

  • SNARE proteins drive intracellular membrane fusion between transport vesicles and organelles.

    “SNARE proteins drive intracellular membrane fusion between transport vesicles and organelles (82).”

    From Computed structures of core eukaryotic protein complexes (2021) · cites this paper as [82]

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Authors
Südhof, T. C., & Rothman, J. E.
Affiliations
  • Department of Cellular and Molecular Physiology, Stanford University, Palo Alto, CA 94304, USA.
  • Yale University (US)
Venue
Science
Published
2009-01-23
Volume
323
Issue
5913
Pages
474-477
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2024136850
Cited by
2,027
References
73
Citations by year
2026: 64 · 2025: 64 · 2024: 76 · 2023: 115 · 2022: 114 · 2021: 105 · 2020: 107 · 2019: 112 · 2018: 113 · 2017: 129 · 2016: 112 · 2015: 140 · 2014: 121 · 2013: 160 · 2012: 150
FWCI
12.50
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of General Medical Sciences (R01GM071458)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
membrane fusion, SNARE proteins, Sm proteins, trans-SNARE complex, synaptic vesicle exocytosis, synaptotagmin, complexin, calcium sensor, neurotransmitter release, vesicle targeting
MeSH terms
Animals, Membrane Fusion, Nerve Tissue Proteins, Synaptic Transmission, Protein Binding, Protein Conformation, Synapses, Synaptic Vesicles, Protein Structure, Tertiary, Amino Acid Motifs, Protein Structure, Quaternary, Vesicular Transport Proteins, SNARE Proteins, Qa-SNARE Proteins, Synaptotagmins, Munc18 Proteins

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