RIM-Binding Protein, a Central Part of the Active Zone, Is Essential for Neurotransmitter Release
RIM-Binding Protein, a Central Part of the Active Zone, Is Essential for Neurotransmitter Release
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DOI：
10.1126/science.1212991
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发表时间：
2011-12-16
期刊：
影响因子：
56.9
通讯作者：
Sigrist, Stephan J.
中科院分区：
文献类型：
--
作者：
Liu, Karen S. Y.;Siebert, Matthias;Sigrist, Stephan J.
在突触前活动区（AZ）膜的突触囊泡（SV）的融合介导的分子机制已被详细研究，并已确定了几个重要的组成部分。AZ相关蛋白支架被视为仅对传输起调节作用。我们发现，果蝇Rab3相互作用分子（RIM）结合蛋白（DRBP）是必不可少的，不仅为AZ支架的完整性，但也为胞吐神经递质的释放。双色受激发射耗尽显微镜显示DRBP包围着中央Ca（2+）通道场。在drbp突变体中，Ca（2+）通道聚集和Ca（2+）内流受损，突触释放概率显著降低。我们的数据确定RBP家族蛋白作为AZ支架的主要效应物，其对于SV、Ca（2+）通道和SV融合机制的偶联是必需的。
The molecular machinery mediating the fusion of synaptic vesicles (SVs) at presynaptic active zone (AZ) membranes has been studied in detail, and several essential components have been identified. AZ-associated protein scaffolds are viewed as only modulatory for transmission. We discovered that Drosophila Rab3-interacting molecule (RIM)-binding protein (DRBP) is essential not only for the integrity of the AZ scaffold but also for exocytotic neurotransmitter release. Two-color stimulated emission depletion microscopy showed that DRBP surrounds the central Ca(2+) channel field. In drbp mutants, Ca(2+) channel clustering and Ca(2+) influx were impaired, and synaptic release probability was drastically reduced. Our data identify RBP family proteins as prime effectors of the AZ scaffold that are essential for the coupling of SVs, Ca(2+) channels, and the SV fusion machinery.