1. RIM binding protein couples synaptic vesicle recruitment to release sites
- Author
-
Markus C. Wahl, Ulrich Stelzl, Sunbin Liu, Stephan J. Sigrist, Martin Lehmann, Janine Lützkendorf, Astrid G. Petzoldt, Benno Kuropka, Vladimir Ugorets, Bernhard Loll, Christine B. Beuschel, Niraja Ramesh, Christian Freund, Torsten W.B. Götz, Elena Knoche, Suneel Reddy-Alla, Jan H. Driller, Sara Mertel, Fan Liu, and Tanja Matkovic-Rachid
- Subjects
Scaffold protein ,Central Nervous System ,Male ,rab3 GTP-Binding Proteins ,Protein domain ,Genetic Vectors ,Nerve Tissue Proteins ,Biology ,Synaptic vesicle ,Synaptic Transmission ,SH3 domain ,Article ,Animals, Genetically Modified ,Cell Signaling ,ddc:570 ,Escherichia coli ,Animals ,Drosophila Proteins ,Protein Interaction Domains and Motifs ,Cloning, Molecular ,Cell signaling, Neuroscience ,active zone organization ,quantal parameters ,cross linking ,ca2 channels ,bruchpilot ,plasticity ,domain ,determines ,assemblies ,MUNC13 1 ,Binding Sites ,Vesicle ,Binding protein ,Membrane Proteins ,Cell Biology ,Recombinant Proteins ,Cell biology ,Fibronectin ,Cytoskeletal Proteins ,Drosophila melanogaster ,Gene Expression Regulation ,Larva ,Synapses ,biology.protein ,Female ,Protein Conformation, beta-Strand ,Calcium Channels ,Synaptic Vesicles ,Carrier Proteins ,Presynaptic active zone ,Protein Binding ,Neuroscience - Abstract
Petzoldt et al. investigate the functional protein architecture at the presynaptic active zone, an elaborate protein scaffold organizing synaptic vesicle (SV) release. They find that the conserved multidomain protein RIM-BP provides a relay to guide SVs during their recruitment into membrane close SV release sites., 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., Graphical Abstract
- Published
- 2020
- Full Text
- View/download PDF