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Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14869-74. doi: 10.1073/pnas.1000606107. Epub 2010 Aug 2.

Differential regulation of synchronous versus asynchronous neurotransmitter release by the C2 domains of synaptotagmin 1.

Author information

  • 1Picower Institute for Learning and Memory, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. motojiro.yoshihara@umassmed.edu

Abstract

Synaptic vesicle fusion at many synapses has been kinetically separated into two distinct Ca(2+)-dependent temporal components consisting of a rapid synchronous phase followed by a slower asynchronous component. Mutations in the synaptic vesicle Ca(2+) sensor Synaptotagmin 1 (Syt 1) reduce synchronous neurotransmission while enhancing the slower asynchronous phase of release. Syt 1 regulation of vesicle fusion requires interactions mediated by its tandem cytoplasmic C2 domains (C2A and C2B). Although Ca(2+) binding by Syt 1 is predicted to drive synchronous release, it is unknown if Ca(2+) interactions with either C2 domain is required for suppression of asynchronous release. To determine if Ca(2+) binding by Syt 1 regulates these two phases of release independently, we performed electrophysiological analysis of transgenically expressed Syt 1 mutated at Ca(2+) binding sites in C2A or C2B in the background of Drosophila Syt 1-null mutants. Transgenic animals expressing mutations that disrupt Ca(2+) binding to C2A fully restored the synchronous phase of neurotransmitter release, whereas the asynchronous component was not suppressed. In contrast, rescue with Ca(2+)-binding mutants in C2B displayed little rescue of the synchronous release component, but reduced asynchronous release. These results suggest that the tandem C2 domains of Syt 1 play independent roles in neurotransmission, as Ca(2+) binding to C2A suppresses asynchronous release, whereas Ca(2+) binding to C2B mediates synchronous fusion.

PMID:
20679236
[PubMed - indexed for MEDLINE]
PMCID:
PMC2930414
Free PMC Article

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