RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 113 |
Issue number | 41 |
Pages (from-to) | 11615-11620 |
Number of pages | 6 |
ISSN | 0027-8424 |
DOIs | |
Publication status | Published - 11 Oct 2016 |
Externally published | Yes |
- 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
Research areas
ID: 334035217