TY  - JOUR
AU  - Grauel, M Katharina
AU  - Maglione, Marta
AU  - Reddy-Alla, Suneel
AU  - Willmes, Claudia G
AU  - Brockmann, Marisa M
AU  - Trimbuch, Thorsten
AU  - Rosenmund, Tanja
AU  - Pangalos, Maria
AU  - Vardar, Gülçin
AU  - Stumpf, Alexander
AU  - Walter, Alexander M
AU  - Rost, Benjamin R
AU  - Eickholt, Britta J
AU  - Haucke, Volker
AU  - Schmitz, Dietmar
AU  - Sigrist, Stephan J
AU  - Rosenmund, Christian
TI  - RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 113
IS  - 41
SN  - 0027-8424
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DZNE-2020-05131
SP  - 11615-11620
PY  - 2016
AB  - 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.
KW  - Action Potentials
KW  - Animals
KW  - Calcium: metabolism
KW  - Calcium Channels: metabolism
KW  - Cells, Cultured
KW  - Electrophysiological Phenomena
KW  - Female
KW  - Gene Deletion
KW  - Gene Expression
KW  - Gene Targeting
KW  - Genetic Loci
KW  - Hippocampus: metabolism
KW  - Male
KW  - Mice
KW  - Mice, Knockout
KW  - Neurons: metabolism
KW  - Phenotype
KW  - Protein Transport
KW  - Synapses: metabolism
KW  - Synaptic Transmission: genetics
KW  - Synaptic Vesicles: metabolism
KW  - Calcium Channels (NLM Chemicals)
KW  - Calcium (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27671655
C2  - pmc:PMC5068320
DO  - DOI:10.1073/pnas.1605256113
UR  - https://pub.dzne.de/record/138809
ER  -