![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (accepted manuscript (final draft))
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
44MB |
| 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., Maglione, M., Reddy-Alla, S., Willmes, C.G., Brockmann, M.M., Trimbuch, T., Rosenmund, T., Pangalos, M., Vardar, G., Stumpf, A., Walter, A.M., Rost, B.R., Eickholt, B.J., Haucke, V., Schmitz, D., 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 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Volume: | 113 |
| Number: | 41 |
| Page Range: | 11615-11620 |
| Date: | 11 October 2016 |
| Official Publication: | https://doi.org/10.1073/pnas.1605256113 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
