Calcium control of neurotransmitter release.

Calcium control of neurotransmitter release.
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神经递质释放的钙控制。

DOI:
10.1101/cshperspect.a011353
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发表时间:
2012-01-01
影响因子:
7.2
通讯作者:
Südhof TC
Südhof TC
中科院分区:
生物学1区
文献类型:
--
作者:
Südhof TC

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当进入突触前末梢时,动作电位打开Ca 2+通道,并瞬时增加突触前活动区的局部Ca 2+浓度。然后,Ca 2+通过激活突触结合蛋白Ca 2+传感器在几百微秒内触发神经递质释放。突触结合蛋白通过两个C2-结构域结合Ca 2+,并将Ca 2+信号转化为膜融合机制的机械激活;这种激活由突触结合蛋白C2-结构域与磷脂和SNARE蛋白的Ca 2+依赖性相互作用介导。在触发胞吐作用时,突触结合蛋白不单独起作用,而是需要称为复合蛋白的强制性辅因子,复合蛋白是一种结合SNARE复合物并同时激活和夹持SNARE复合物的小蛋白,从而定位SNARE复合物用于随后的突触结合蛋白作用。突触结合蛋白和复合蛋白的保守功能通常在大多数(如果不是全部的话)Ca 2+调节的整个身体的胞吐形式中起作用,包括肥大细胞的脱粒、精子细胞中的顶体胞吐、内分泌细胞的激素分泌和神经肽释放。
Upon entering a presynaptic terminal, an action potential opens Ca2+-channels, and transiently increases the local Ca2+-concentration at the presynaptic active zone. Ca2+ then triggers neurotransmitter release within a few hundred microseconds by activating synaptotagmin Ca2+-sensors. Synaptotagmins bind Ca2+ via two C2-domains, and transduce the Ca2+-signal into a mechanical activation of the membrane fusion machinery; this activation is mediated by the Ca2+-dependent interaction of the synaptotagmin C2-domains with phospholipids and SNARE proteins. In triggering exocytosis, synaptotagmins do not act alone, but require an obligatory co-factor called complexin, a small protein that binds to SNARE complexes and simultaneously activates and clamps the SNARE complexes, thereby positioning the SNARE complexes for subsequent synaptotagmin action. The conserved function of synaptotagmins and complexins operates generally in most, if not all, Ca2+-regulated forms of exocytosis throughout the body, including degranulation of mast-cells, acrosome exocytosis in sperm cells, hormone secretion from endocrine cells, and neuropeptide release.
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