Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release

Jun Xu, Zhiping P. Pang, Ok Ho Shin, Thomas C. Südhof

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Spontaneous 'mini' release occurs at all synapses, but its nature remains enigmatic. We found that 95% of spontaneous release in murine cortical neurons was induced by Ca 2+-binding to synaptotagmin-1 (Syt1), the Ca 2 + sensor for fast synchronous neurotransmitter release. Thus, spontaneous and evoked release used the same Ca 2+ -dependent release mechanism. As a consequence, Syt1 mutations that altered its Ca 2+ affinity altered spontaneous and evoked release correspondingly. Paradoxically, Syt1 deletions (as opposed to point mutations) massively increased spontaneous release. This increased spontaneous release remained Ca 2+ dependent but was activated at lower Ca 2+concentrations and with a lower Ca 2 + cooperativity than synaptotagmin-driven spontaneous release. Thus, in addition to serving as a Ca 2+ senso r for spontaneous and evoked release, Syt1 clamped a second, more sensitive Ca 2+ sensor for spontaneous release that resembles the Ca 2+ sensor for evoked asynchronous release. These data suggest that Syt1 controls both evoked and spontaneous release at a synapse as a simultaneous Ca 2+ -dependent activator and clamp of exocytosis.

Original languageEnglish (US)
Pages (from-to)759-766
Number of pages8
JournalNature Neuroscience
Volume12
Issue number6
DOIs
StatePublished - Jun 2009

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Synaptotagmin I
Synapses
Synaptotagmin II
Exocytosis
Point Mutation
Neurotransmitter Agents
Neurons
Mutation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Xu, J., Pang, Z. P., Shin, O. H., & Südhof, T. C. (2009). Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release. Nature Neuroscience, 12(6), 759-766. https://doi.org/10.1038/nn.2320

Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release. / Xu, Jun; Pang, Zhiping P.; Shin, Ok Ho; Südhof, Thomas C.

In: Nature Neuroscience, Vol. 12, No. 6, 06.2009, p. 759-766.

Research output: Contribution to journalArticle

Xu, J, Pang, ZP, Shin, OH & Südhof, TC 2009, 'Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release', Nature Neuroscience, vol. 12, no. 6, pp. 759-766. https://doi.org/10.1038/nn.2320
Xu, Jun ; Pang, Zhiping P. ; Shin, Ok Ho ; Südhof, Thomas C. / Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release. In: Nature Neuroscience. 2009 ; Vol. 12, No. 6. pp. 759-766.
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