Synaptotagmin-1 and Synaptotagmin-7 Trigger Synchronous and Asynchronous Phases of Neurotransmitter Release

Taulant Bacaj, Dick Wu, Xiaofei Yang, Wade Morishita, Peng Zhou, Wei Xu, Robert C. Malenka, Thomas C. Südhof

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

In forebrain neurons, knockout of synaptotagmin-1 blocks fast Ca2+-triggered synchronous neurotransmitter release but enables manifestation of slow Ca2+-triggered asynchronous release. Here, we show using single-cell PCR that individual hippocampal neurons abundantly coexpress two Ca2+-binding synaptotagmin isoforms, synaptotagmin-1 and synaptotagmin-7. In synaptotagmin-1-deficient synapses of excitatory and inhibitory neurons, loss of function of synaptotagmin-7 suppressed asynchronous release. This phenotype was rescued by wild-type but not mutant synaptotagmin-7 lacking functional Ca2+-binding sites. Even in synaptotagmin-1-containing neurons, synaptotagmin-7 ablation partly impaired asynchronous release induced by extended high-frequency stimulus trains. Synaptotagmins bind Ca2+ via two C2 domains, the C2A and C2B domains. Surprisingly, synaptotagmin-7 function selectively required its C2A domain Ca2+-binding sites, whereas synaptotagmin-1 function required its C2B domain Ca2+-binding sites. Our data show that nearly all Ca2+-triggered release at a synapse is due to synaptotagmins, with synaptotagmin-7 mediating a slower form of Ca2+-triggered release that is normally occluded by faster synaptotagmin-1-induced release but becomes manifest upon synaptotagmin-1 deletion.

Original languageEnglish (US)
Pages (from-to)947-959
Number of pages13
JournalNeuron
Volume80
Issue number4
DOIs
StatePublished - Nov 20 2013

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Synaptotagmin I
Synaptotagmins
Neurotransmitter Agents
Neurons
Binding Sites
Synapses
Prosencephalon
Protein Isoforms

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Synaptotagmin-1 and Synaptotagmin-7 Trigger Synchronous and Asynchronous Phases of Neurotransmitter Release. / Bacaj, Taulant; Wu, Dick; Yang, Xiaofei; Morishita, Wade; Zhou, Peng; Xu, Wei; Malenka, Robert C.; Südhof, Thomas C.

In: Neuron, Vol. 80, No. 4, 20.11.2013, p. 947-959.

Research output: Contribution to journalArticle

Bacaj, T, Wu, D, Yang, X, Morishita, W, Zhou, P, Xu, W, Malenka, RC & Südhof, TC 2013, 'Synaptotagmin-1 and Synaptotagmin-7 Trigger Synchronous and Asynchronous Phases of Neurotransmitter Release', Neuron, vol. 80, no. 4, pp. 947-959. https://doi.org/10.1016/j.neuron.2013.10.026
Bacaj, Taulant ; Wu, Dick ; Yang, Xiaofei ; Morishita, Wade ; Zhou, Peng ; Xu, Wei ; Malenka, Robert C. ; Südhof, Thomas C. / Synaptotagmin-1 and Synaptotagmin-7 Trigger Synchronous and Asynchronous Phases of Neurotransmitter Release. In: Neuron. 2013 ; Vol. 80, No. 4. pp. 947-959.
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