Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305.
Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305.
Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):E8081-E8090. doi: 10.1073/pnas.1702991114. Epub 2017 Sep 5.
Fast neurotransmitter release from ribbon synapses via Ca-triggered exocytosis requires tight coupling of L-type Ca channels to release-ready synaptic vesicles at the presynaptic active zone, which is localized at the base of the ribbon. Here, we used genetic, electrophysiological, and ultrastructural analyses to probe the architecture of ribbon synapses by perturbing the function of RIM-binding proteins (RBPs) as central active-zone scaffolding molecules. We found that genetic deletion of RBP1 and RBP2 did not impair synapse ultrastructure of ribbon-type synapses formed between rod bipolar cells (RBCs) and amacrine type-2 (AII) cells in the mouse retina but dramatically reduced the density of presynaptic Ca channels, decreased and desynchronized evoked neurotransmitter release, and rendered evoked and spontaneous neurotransmitter release sensitive to the slow Ca buffer EGTA. These findings suggest that RBPs tether L-type Ca channels to the active zones of ribbon synapses, thereby synchronizing vesicle exocytosis and promoting high-fidelity information transfer in retinal circuits.
通过 Ca2+触发的胞吐作用从带状突触快速释放神经递质需要将 L 型 Ca2+通道与位于带状突触底部的准备释放的突触小泡紧密偶联，该部位位于突触前活性区。在这里，我们通过干扰 RIM 结合蛋白（RBPs）的功能（作为中央活性区支架分子），使用遗传、电生理和超微结构分析来探测带状突触的结构。我们发现，RBP1 和 RBP2 的基因缺失并不损害在小鼠视网膜中的 rod 双极细胞（RBC）和amacrine 型 2（AII）细胞之间形成的带状型突触的突触超微结构，但大大降低了突触前 Ca2+通道的密度，减少和去同步化诱发的神经递质释放，并使诱发和自发的神经递质释放对慢 Ca2+缓冲剂 EGTA 敏感。这些发现表明，RBPs 将 L 型 Ca2+通道固定在带状突触的活性区，从而使囊泡胞吐作用同步，并促进视网膜回路中高保真信息传递。
