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@ARTICLE{Grauel:138809,
author = {Grauel, M Katharina and Maglione, Marta and Reddy-Alla,
Suneel and Willmes, Claudia G and Brockmann, Marisa M and
Trimbuch, Thorsten and Rosenmund, Tanja and Pangalos, Maria
and Vardar, Gülçin and Stumpf, Alexander and Walter,
Alexander M and Rost, Benjamin R and Eickholt, Britta J and
Haucke, Volker and Schmitz, Dietmar and Sigrist, Stephan J
and Rosenmund, Christian},
title = {{RIM}-binding protein 2 regulates release probability by
fine-tuning calcium channel localization at murine
hippocampal synapses.},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {113},
number = {41},
issn = {0027-8424},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {DZNE-2020-05131},
pages = {11615-11620},
year = {2016},
abstract = {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.},
keywords = {Action Potentials / Animals / Calcium: metabolism / Calcium
Channels: metabolism / Cells, Cultured /
Electrophysiological Phenomena / Female / Gene Deletion /
Gene Expression / Gene Targeting / Genetic Loci /
Hippocampus: metabolism / Male / Mice / Mice, Knockout /
Neurons: metabolism / Phenotype / Protein Transport /
Synapses: metabolism / Synaptic Transmission: genetics /
Synaptic Vesicles: metabolism / Calcium Channels (NLM
Chemicals) / Calcium (NLM Chemicals)},
cin = {AG Schmitz 1},
ddc = {500},
cid = {I:(DE-2719)1810004},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27671655},
pmc = {pmc:PMC5068320},
doi = {10.1073/pnas.1605256113},
url = {https://pub.dzne.de/record/138809},
}