RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses
| Autor: | Dietmar Schmitz, Rosenmund T, Gülçin Vardar, Claudia G Willmes, Alexander Stumpf, Marta Maglione, Alexander M. Walter, Marisa M Brockmann, Benjamin R. Rost, Haucke, Stephan J. Sigrist, Suneel Reddy-Alla, Christian Rosenmund, Thorsten Trimbuch, Britta J. Eickholt, Maria Pangalos, Grauel Mk |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Action Potentials Gene Expression metabolism [Hippocampus] Hippocampal formation Hippocampus Synaptic Transmission Mice chemistry.chemical_compound metabolism [Calcium] Neurotransmitter Cells Cultured Mice Knockout Neurons Multidisciplinary metabolism [Calcium Channels] Biological Sciences Transport protein Cell biology Protein Transport Phenotype metabolism [Neurons] Gene Targeting Female ddc:500 Synaptic Vesicles genetics [Synaptic Transmission] Gene isoform Neural facilitation Biology Neurotransmission Synaptic vesicle 03 medical and health sciences Animals metabolism [Synaptic Vesicles] Calcium channel metabolism [Synapses] Electrophysiological Phenomena 030104 developmental biology chemistry Genetic Loci Synapses Calcium sense organs Calcium Channels Neuroscience Gene Deletion |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 113(41): 11615–11620 Proceedings of the National Academy of Sciences of the United States of America 113(41), 11615-11620 (2016). doi:10.1073/pnas.1605256113 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1605256113 |
| Popis: | Significance Highly regulated and precise positioning of Ca 2+ channels at the active zone (AZ) controls Ca 2+ nanodomains at release sites. Their exact localization affects vesicular release probability (P VR ) and is important for proper synaptic transmission during repetitive stimulation. We provide a detailed analysis of synaptic transmission combined with superresolution imaging of the AZ organization in mouse hippocampal synapses lacking Rab-interacting molecule-binding protein 2 (RIM-BP2). By dual- and triple-channel time-gated stimulated emission depletion (gSTED) microscopy, we directly show that RIM-BP2 fine-tunes voltage-gated Ca 2+ channel 2.1 (Ca V 2.1) localization at the AZ. We reveal that RIM-BP2 likely regulates the Ca 2+ nanodomain by positioning Ca V 2.1 channels close to synaptic vesicle release sites. Loss of RIM-BP2 reduces P VR and alters short-term plasticity. |
| Databáze: | OpenAIRE |
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