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标题：Differential regulation of synchronous versus asynchronous neurotransmitter release by the C2 domains of synaptotagmin 1
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作者：Motojiro Yoshihara ; Zhuo Guan ; J. Troy Littleton 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：33
页码：14869-14874
DOI：10.1073/pnas.1000606107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Synaptic vesicle fusion at many synapses has been kinetically separated into two distinct Ca2+-dependent temporal components consisting of a rapid synchronous phase followed by a slower asynchronous component. Mutations in the synaptic vesicle Ca2+ 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 Ca2+ binding by Syt 1 is predicted to drive synchronous release, it is unknown if Ca2+ interactions with either C2 domain is required for suppression of asynchronous release. To determine if Ca2+ binding by Syt 1 regulates these two phases of release independently, we performed electrophysiological analysis of transgenically expressed Syt 1 mutated at Ca2+ binding sites in C2A or C2B in the background of Drosophila Syt 1-null mutants. Transgenic animals expressing mutations that disrupt Ca2+ binding to C2A fully restored the synchronous phase of neurotransmitter release, whereas the asynchronous component was not suppressed. In contrast, rescue with Ca2+-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 Ca2+ binding to C2A suppresses asynchronous release, whereas Ca2+ binding to C2B mediates synchronous fusion.
关键词：Drosophila ; neuromuscular junction ; synaptic transmission ; electrophysiology