高锶离子亲和力传感蛋白介导CALYX突触囊泡异步和自发释放

突触囊泡在钙离子(Ca2+)触发下释放神经递质普遍存在着同步和异步两种形式.突触囊泡膜蛋白(synaptotagmin 2,Syt-2)已被证实是Calyx of Held突触囊泡同步释放的Ca2+传感蛋白,而相关的异步释放Ca2+传感蛋白还有待于探索.虽然锶离子(Sr2+)因其物理和化学性质都接近Ca2+,且能触发更多的囊泡异步释放成分而成为研究异步释放机制的常用工具,但有关Sr2+触发异步释放的机制存在着争议.本文在胞外以Sr2+替换Ca2+的条件下,通过对野生型(WT)和Syt-2敲除型(Z2B-/-)小鼠Calyx突触囊泡自发和诱发释放的电生理特性分析,发现Syt-2是介导Sr2+诱发的突触囊泡快速释放的传感蛋白,但不是介导Sr2+相关神经递质异步释放和自发释放的传感蛋白;而未知的触发囊泡异步释放的传感蛋白相比Syt-2对Sr2+具有更高的亲和力,同时也介导突触囊泡的自发释放.这一研究为探索并最终发现触发囊泡异步释放的未知传感蛋白提供了新的线索.

Ca2+ Sensor for Asynchronous Vesicle Release Has High-affinity to Sr2 and Mediates Spontaneous Release at The Calyx of Held Synapses

The kinetics of Ca²⁺ triggered synaptic vesicle fusion contains synchronous and asynchronous components. At the Calyx of Held synapse, synaptotagmin-2 has been identified as the Ca² sensor protein for synchronous vesicle release while the Ca² sensor for asynchronous vesicle release remains unknown. Sr² is a divalent cation similar in size to Ca² and often substituted for Ca² as a tool in studying asynchronous vesicle release. However, the mechanism of Sr² triggering vesicle release is still under debate. We studied the spontaneous and evoked vesicle release at the wild type and synaptotagmin-2 knock-out calyceal synapses in the existence of extracellular Sr² and found synaptotagmin-2 only mediates the Sr² triggered synchronous vesicle release but not the asynchronous and spontaneous release; the unknown divalent sensor for asynchronous vesicle release has high-affinity to Sr² and mediates the spontaneous vesicle release. Our study provided a new insight into exploring the divalent sensor in triggering asynchronous synaptic vesicle release.