At presynaptic active zones, arrays of large conserved scaffold proteins mediate fast and temporally precise release of synaptic vesicles (SVs). SV release sites could be identified by clusters of Munc13, which allow SVs to dock in defined nanoscale relation to Ca2+ channels. We here show in Drosophila that RIM-binding protein (RIM-BP) connects release sites physically and functionally to the ELKS family Bruchpilot (BRP)-based scaffold engaged in SV recruitment. The RIM-BP N-terminal domain, while dispensable for SV release site organization, was crucial for proper nanoscale patterning of the BRP scaffold and needed for SV recruitment of SVs under strong stimulation. Structural analysis further showed that the RIM-BP fibronectin domains form a “hinge” in the protein center, while the C-terminal SH3 domain tandem binds RIM, Munc13, and Ca2+ channels release machinery collectively. RIM-BPs’ conserved domain architecture seemingly provides a relay to guide SVs from membrane far scaffolds into membrane close release sites.

中文翻译：

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RIM 结合蛋白将突触小泡招募到释放位点

在突触前活性区，大量保守的支架蛋白阵列介导突触小泡（SV）的快速且时间精确的释放。SV 释放位点可以通过 Munc13 簇来识别，这使得 SV 能够以定义的纳米级关系与 Ca2+ 通道对接。我们在果蝇中展示了 RIM 结合蛋白 (RIM-BP) 在物理和功能上将释放位点连接到参与 SV 招募的基于 ELKS 家族 Bruchpilot (BRP) 的支架。RIM-BP N 端结构域虽然对于 SV 释放位点组织来说是可有可无的，但对于 BRP 支架的适当纳米级图案化至关重要，并且是强刺激下 SV 招募 SV 所必需的。结构分析进一步表明，RIM-BP 纤连蛋白结构域在蛋白质中心形成“铰链”，而 C 端 SH3 结构域串联结合 RIM、Munc13 和 Ca2+ 通道释放机制。RIM-BP 的保守结构域结构似乎提供了一个中继，引导 SV 从膜远支架进入膜近释放位点。