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Cited by 107Cellular transport and secretionLipid Membrane Structure and BehaviorNeuroscience and Neuropharmacology Research

Single-Molecule Studies of the Neuronal SNARE Fusion Machinery

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Brunger, Axel T., Weninger, Keith, Bowen, Mark, Chu, Steven·2009·Annual Review of Biochemistry
DOI 10.1146/annurev.biochem.77.070306.103621PMC PMC2854664
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Abstract

SNAREs are essential components of the machinery for Ca 2+-triggered fusion of synaptic vesicles with the plasma membrane, resulting in neurotransmitter release into the synaptic cleft. Although much is known about their biophysical and structural properties and their interactions with accessory proteins such as the Ca 2+ sensor synaptotagmin, their precise role in membrane fusion remains an enigma. Ensemble studies of liposomes with reconstituted SNAREs have demonstrated that SNAREs and accessory proteins can trigger lipid mixing/fusion, but the inability to study individual fusion events has precluded molecular insights into the fusion process. Thus, this field is ripe for studies with single-molecule methodology. In this review, we discuss applications of single-molecule approaches to observe reconstituted SNAREs, their complexes, associated proteins, and their effect on biological membranes. Some of the findings are provocative, such as the possibility of parallel and antiparallel SNARE complexes or of vesicle docking with only syntaxin and synaptobrevin, but have been confirmed by other experiments.

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  • Munc13 opens syntaxin-1, allowing trans-zippering of SNAREs from the N- to C-terminals and formation of a 4-helix trans-complex or ternary complex.

    “Munc13 opens syntaxin-1 (407), allowing the trans-zippering of the SNAREs in the plasma and granular membranes from the N- to the C-terminals (which are anchored to the membrane). This leads to the formation of a 4-helix trans-complex, also referred to as the ‘ternary complex’ (100) (Figure 16B, step ii).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [100]

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Sorted by citations

Authors
Brunger, A. T., Weninger, K., Bowen, M., & Chu, S.
Affiliations
  • The Howard Hughes Medical Institute and Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Structural Biology, and Photon Science, Stanford University, California 94305;
  • North Carolina State University (US)
  • Stony Brook University Hospital (US)
  • United States Department of Energy (US)
ORCID
Venue
Annual Review of Biochemistry
Publisher
Annual Reviews
Published
2009-06-01
Volume
78
Issue
1
Pages
903-928
ISSN
  • 0066-4154 (ISSN-L)
  • 1545-4509
DOI
10.1146/annurev.biochem.77.070306.103621
PMC
PMC2854664
OpenAlex
W2134371594
Cited by
107
References
4
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 9 · 2014: 10 · 2013: 11 · 2012: 10
FWCI
1.04
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Mental Health (1-R01-MH63105, MH 081923-01, R01MH081923, R37MH063105, R01MH063105)
  • National Institute of General Medical Sciences (R21GM076039, GM 076039)
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 › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
SNARE proteins, synaptic vesicle fusion, neurotransmitter release, synaptotagmin, syntaxin, synaptobrevin, single-molecule analysis, lipid mixing, membrane fusion, vesicle docking
MeSH terms
Animals, Fluorescence, Humans, Neurons, Spectrum Analysis, Microscopy, Atomic Force, SNARE Proteins, Synaptotagmins

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