Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam and VU Medical Center, 1081 HV Amsterdam, The Netherlands.
Trends Neurosci. 2011 Sep;34(9):487-97. doi: 10.1016/j.tins.2011.07.003. Epub 2011 Aug 9.
Regulated neurotransmitter secretion depends on Ca(2+) sensors, C2 domain proteins that associate with phospholipids and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) complexes to trigger release upon Ca(2+) binding. Ca(2+) sensors are thought to prevent spontaneous fusion at rest (clamping) and to promote fusion upon Ca(2+) activation. At least eight, often coexpressed, Ca(2+) sensors have been identified in mammals. Accumulating evidence suggests that multiple Ca(2+) sensors interact, rather than work autonomously, to produce the complex secretory response observed in neurons and secretory cells. In this review, we present several working models to describe how different sensors might be arranged to mediate synchronous, asynchronous and spontaneous neurotransmitter release. We discuss the scenario that different Ca(2+) sensors typically act on one shared vesicle pool and compete for binding the multiple SNARE complexes that are likely to assemble at single vesicles, to exert both clamping and fusion-promoting functions.
受调控的神经递质分泌依赖于钙（Ca2+）传感器，C2 结构域蛋白与磷脂和可溶性 N-乙基马来酰亚胺敏感的融合蛋白附着蛋白受体（SNARE）复合物结合，在 Ca2+结合时触发释放。钙（Ca2+）传感器被认为可以防止在静止（钳位）时自发融合，并在 Ca2+激活时促进融合。在哺乳动物中已经鉴定出至少八种，通常是共表达的，钙（Ca2+）传感器。越来越多的证据表明，多个钙（Ca2+）传感器相互作用，而不是自主工作，以产生在神经元和分泌细胞中观察到的复杂分泌反应。在这篇综述中，我们提出了几个工作模型来描述不同的传感器如何排列以介导同步、异步和自发的神经递质释放。我们讨论了这样一种情况，即不同的钙（Ca2+）传感器通常作用于一个共享的囊泡池，并竞争结合可能在单个囊泡上组装的多个 SNARE 复合物，以发挥钳位和促进融合的功能。
