RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses

Medientyp: E-Artikel

Titel: RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses

Beteiligte: Grauel, M. Katharina; Maglione, Marta; Reddy-Alla, Suneel; Willmes, Claudia G.; Brockmann, Marisa M.; Trimbuch, Thorsten; Rosenmund, Tanja; Pangalos, Maria; Vardar, Gülçin; Stumpf, Alexander; Walter, Alexander M.; Rost, Benjamin R.; Eickholt, Britta J.; Haucke, Volker; Schmitz, Dietmar; Sigrist, Stephan J.; Rosenmund, Christian

Erschienen: National Academy of Sciences, 2016

Sprache: Englisch

ISSN: 0027-8424; 1091-6490

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Beschreibung: 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.

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