
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.
genetics [Synaptic Transmission], Male, Action Potentials, Gene Expression, metabolism [Hippocampus], Hippocampus, Synaptic Transmission, Mice, Animals, metabolism [Calcium], metabolism [Synaptic Vesicles], Cells, Cultured, Mice, Knockout, Neurons, metabolism [Calcium Channels], metabolism [Synapses], Electrophysiological Phenomena, Protein Transport, Phenotype, metabolism [Neurons], Genetic Loci, Gene Targeting, Synapses, Calcium, Female, Calcium Channels, Function and Dysfunction of the Nervous System, Gene Deletion, Neuroscience, ddc: ddc:500
genetics [Synaptic Transmission], Male, Action Potentials, Gene Expression, metabolism [Hippocampus], Hippocampus, Synaptic Transmission, Mice, Animals, metabolism [Calcium], metabolism [Synaptic Vesicles], Cells, Cultured, Mice, Knockout, Neurons, metabolism [Calcium Channels], metabolism [Synapses], Electrophysiological Phenomena, Protein Transport, Phenotype, metabolism [Neurons], Genetic Loci, Gene Targeting, Synapses, Calcium, Female, Calcium Channels, Function and Dysfunction of the Nervous System, Gene Deletion, Neuroscience, ddc: ddc:500
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