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RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses

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Item Type:Article
Title:RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses
Creators Name:Grauel, M.K. and Maglione, M. and Reddy-Alla, S. and Willmes, C.G. and Brockmann, M.M. and Trimbuch, T. and Rosenmund, T. and Pangalos, M. and Vardar, G. and Stumpf, A. and Walter, A.M. and Rost, B.R. and Eickholt, B.J. and Haucke, V. and Schmitz, D. and Sigrist, S.J. and Rosenmund, C.
Abstract:The tight spatial coupling of synaptic vesicles and voltage-gated Ca(2+) channels (CaVs) ensures efficient action potential-triggered neurotransmitter release from presynaptic active zones (AZs). Rab-interacting molecule-binding proteins (RIM-BPs) interact with Ca(2+) channels and via RIM with other components of the release machinery. Although human RIM-BPs have been implicated in autism spectrum disorders, little is known about the role of mammalian RIM-BPs in synaptic transmission. We investigated RIM-BP2-deficient murine hippocampal neurons in cultures and slices. Short-term facilitation is significantly enhanced in both model systems. Detailed analysis in culture revealed a reduction in initial release probability, which presumably underlies the increased short-term facilitation. Superresolution microscopy revealed an impairment in CaV2.1 clustering at AZs, which likely alters Ca(2+) nanodomains at release sites and thereby affects release probability. Additional deletion of RIM-BP1 does not exacerbate the phenotype, indicating that RIM-BP2 is the dominating RIM-BP isoform at these synapses.
Keywords:RIM-BP2, Calcium Channel Coupling, Release Probability, Short-Term Plasticity, Active Zone Structure, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:11615-11620
Date:11 October 2016
Official Publication:https://doi.org/10.1073/pnas.1605256113
PubMed:View item in PubMed

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