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Cited by 1,197Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

Neurotransmitter Release: The Last Millisecond in the Life of a Synaptic Vesicle

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Südhof, Thomas C.·2013·Neuron
DOI 10.1016/j.neuron.2013.10.022PMC PMC3866025
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Abstract

During an action potential, Ca(2+) entering a presynaptic terminal triggers synaptic vesicle exocytosis and neurotransmitter release in less than a millisecond. How does Ca(2+) stimulate release so rapidly and precisely? Work over the last decades revealed that Ca(2+) binding to synaptotagmin triggers release by stimulating synaptotagmin binding to a core fusion machinery composed of SNARE and SM proteins that mediates membrane fusion during exocytosis. Complexin adaptor proteins assist synaptotagmin by activating and clamping this core fusion machinery. Synaptic vesicles containing synaptotagmin are positioned at the active zone, the site of vesicle fusion, by a protein complex containing RIM proteins. RIM proteins activate docking and priming of synaptic vesicles and simultaneously recruit Ca(2+) channels to active zones, thereby connecting in a single complex primed synaptic vesicles to Ca(2+) channels. This architecture allows direct flow of Ca(2+) ions from Ca(2+) channels to synaptotagmin, which then triggers fusion, thus mediating tight millisecond coupling of an action potential to neurotransmitter release.

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Cited by

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Authors
Südhof, T. C.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Südhof, Thomas C.
ORCID
Südhof, Thomas C.
Venue
Neuron
Publisher
Elsevier BV
Published
2013-10
Volume
80
Issue
3
Pages
675-690
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2013.10.022
PMC
PMC3866025
OpenAlex
W2060384627
Cited by
1,197
References
16
Citations by year
2026: 84 · 2025: 89 · 2024: 119 · 2023: 83 · 2022: 89 · 2021: 93 · 2020: 94 · 2019: 84 · 2018: 103 · 2017: 120 · 2016: 70 · 2015: 103 · 2014: 64 · 2013: 1
FWCI
9.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Mental Health (P50MH086403)
  • National Institute on Drug Abuse (R01DA030379)
  • National Institute of Neurological Disorders and Stroke (R01NS077906)
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
neurotransmitter release, synaptic vesicle exocytosis, calcium-triggered fusion, synaptotagmin, SNARE proteins, Sm proteins, complexin, active zone, calcium channels, vesicle priming, presynaptic terminals
MeSH terms
Animals, Membrane Fusion, Models, Neurological, Synaptic Transmission, Neurons, Synaptic Vesicles, Neurotransmitter Agents, SNARE Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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