文章基本信息

标题：Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
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作者：Erica Tagliatti ; Oscar D. Bello ; Philipe R. F. Mendonça 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：2020
卷号：117
期号：7
页码：3819-3827
DOI：10.1073/pnas.1920403117
出版社：The National Academy of Sciences of the United States of America
摘要：Synaptotagmin 1 (Syt1) synchronizes neurotransmitter release to action potentials (APs) acting as the fast Ca 2+ release sensor and as the inhibitor (clamp) of spontaneous and delayed asynchronous release. While the Syt1 Ca 2+ activation mechanism has been well-characterized, how Syt1 clamps transmitter release remains enigmatic. Here we show that C2B domain-dependent oligomerization provides the molecular basis for the Syt1 clamping function. This follows from the investigation of a designed mutation (F349A), which selectively destabilizes Syt1 oligomerization. Using a combination of fluorescence imaging and electrophysiology in neocortical synapses, we show that Syt1 F349A is more efficient than wild-type Syt1 (Syt1 WT ) in triggering synchronous transmitter release but fails to clamp spontaneous and synaptotagmin 7 (Syt7)-mediated asynchronous release components both in rescue (Syt1 −/− knockout background) and dominant-interference (Syt1 +/+ background) conditions. Thus, we conclude that Ca 2+ -sensitive Syt1 oligomers, acting as an exocytosis clamp, are critical for maintaining the balance among the different modes of neurotransmitter release..
关键词：synaptic transmission ; synaptotagmin ; C2B domain ; fusion clamp