RIM-binding protein couples synaptic vesicle recruitment to release sites.
Petzoldt, Astrid G. and Götz, Torsten W.B. and Driller, Jan Heiner and Lützkendorf, Janine and Reddy-Alla, Suneel and Matkovic-Rachid, Tanja and Liu, Sunbin and Knoche, Elena and Mertel, Sara and Ugorets Vladimir and Lehmann, Martin and Ramesh, Niraja and Beuschel, Christine Brigitte and Kuropka, Benno and Freund, Christian and Stelzl, Ulrich and Loll, Bernhard and Liu, Fan and Wahl, Markus C. and Sigrist, Stephan J. – 2020
"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."