%0 Journal Article
%A Grauel, M Katharina
%A Maglione, Marta
%A Reddy-Alla, Suneel
%A Willmes, Claudia G
%A Brockmann, Marisa M
%A Trimbuch, Thorsten
%A Rosenmund, Tanja
%A Pangalos, Maria
%A Vardar, Gülçin
%A Stumpf, Alexander
%A Walter, Alexander M
%A Rost, Benjamin R
%A Eickholt, Britta J
%A Haucke, Volker
%A Schmitz, Dietmar
%A Sigrist, Stephan J
%A Rosenmund, Christian
%T RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses.
%J Proceedings of the National Academy of Sciences of the United States of America
%V 113
%N 41
%@ 0027-8424
%C Washington, DC
%I National Acad. of Sciences
%M DZNE-2020-05131
%P 11615-11620
%D 2016
%X The tight spatial coupling of synaptic vesicles and voltage-gated Ca2+ channels (CaVs) ensures efficient action potential-triggered neurotransmitter release from presynaptic active zones (AZs). Rab-interacting molecule-binding proteins (RIM-BPs) interact with Ca2+ 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 Ca2+ 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.
%K Action Potentials
%K Animals
%K Calcium: metabolism
%K Calcium Channels: metabolism
%K Cells, Cultured
%K Electrophysiological Phenomena
%K Female
%K Gene Deletion
%K Gene Expression
%K Gene Targeting
%K Genetic Loci
%K Hippocampus: metabolism
%K Male
%K Mice
%K Mice, Knockout
%K Neurons: metabolism
%K Phenotype
%K Protein Transport
%K Synapses: metabolism
%K Synaptic Transmission: genetics
%K Synaptic Vesicles: metabolism
%K Calcium Channels (NLM Chemicals)
%K Calcium (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:27671655
%2 pmc:PMC5068320
%R 10.1073/pnas.1605256113
%U https://pub.dzne.de/record/138809