Department of Genetics, Institute for Biology, Free University Berlin, 14195 Berlin, Germany.
Science. 2011 Dec 16;334(6062):1565-9. doi: 10.1126/science.1212991.
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.
介导突触小泡（SVs）在突触前活性区（AZ）膜融合的分子机制已被详细研究，并且已经鉴定出了几个关键的组成部分。AZ 相关蛋白支架被认为仅对传递起调节作用。我们发现果蝇 Rab3 相互作用分子（RIM）结合蛋白（DRBP）不仅对 AZ 支架的完整性是必需的，而且对胞吐神经递质释放也是必需的。双色受激发射损耗显微镜显示，DRBP 环绕中央 Ca(2+)通道场。在 drbp 突变体中，Ca(2+)通道聚集和 Ca(2+)内流受损，突触释放概率急剧降低。我们的数据将 RBP 家族蛋白鉴定为 AZ 支架的主要效应物，对于 SVs、Ca(2+)通道和 SV 融合机制的偶联是必需的。
