Autonomous Function of Synaptotagmin 1 in Triggering Synchronous Release Independent of Asynchronous Release
Open accessAbstract
Ca(2+) triggers neurotransmitter release in at least two principal modes, synchronous and asynchronous release. Synaptotagmin 1 functions as a Ca(2+) sensor for synchronous release, but its role in asynchronous release remains unclear. We now show that in cultured cortical neurons stimulated at low frequency ( or Hz), deletion of synaptotagmin 1 also alters only synchronous, not asynchronous, release during the stimulus train, but dramatically enhances "delayed asynchronous release" following the stimulus train. Thus synaptotagmin 1 functions as an autonomous Ca(2+) sensor independent of asynchronous release during isolated action potentials and action potential trains, but restricts asynchronous release induced by residual Ca(2+) after action potential trains. We propose that synaptotagmin 1 occupies release "slots" at the active zone, possibly in a Ca(2+)-independent complex with SNARE proteins that are freed when action potential-induced Ca(2+) influx activates synaptotagmin 1.
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Syt1 also clamps the frequency of miniature spontaneous events.
“In addition to its role in evoked synchronous release, Syt1 also clamps the frequency of miniature spontaneous events11–13.”
From Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis (2015) · cites this paper as [12]
The primary Syt1-SNARE interface is critical for the role of Syt1 as a Ca2+ sensor of evoked release, but is not required for spontaneous release in neurons.
“Together, these observations support the notion that the primary Syt1-SNARE interface is critical for the role of Syt1 as a Ca2+ sensor of evoked release, but that this Syt1-SNARE interface is not required for spontaneous release in neurons, consistent with the differential effect of Syt1 mutations on spontaneous and evoked release11–13.”
From Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis (2015) · cites this paper as [12]
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- Authors
- Maximov, A., & Südhof, T. C.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Südhof, Thomas C.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 48
- Issue
- 4
- Pages
- 547-554
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2037168572
- Cited by
- 238
- References
- 1
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 7 · 2017: 12 · 2016: 11 · 2015: 17 · 2014: 12 · 2013: 17 · 2012: 16
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2815 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- 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 › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- synaptotagmin-1, asynchronous release, calcium sensor, action potential trains, active zone, SNARE proteins, calcium influx, cortical neurons, synaptic vesicle release
- MeSH terms
- Animals, Calcium, Cells, Cultured, Cerebral Cortex, Egtazic Acid, Electric Stimulation, Ionophores, Nerve Endings, Neural Inhibition, Synaptic Transmission, Neurons, Synapses, Time Factors, Ionomycin, Mice, Knockout, Neurotransmitter Agents, Excitatory Postsynaptic Potentials, Synaptotagmin I, Mice
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