Journal Article

DZNE-2020-05131

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses.

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.DZNE* ; Eickholt, B. J. ; Haucke, V. ; Schmitz, D.DZNE* ; Sigrist, S. J. ; Rosenmund, C. (Corresponding author)

2016
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.1605256113

Abstract: 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.

Keyword(s): Action Potentials (MeSH) ; Animals (MeSH) ; Calcium: metabolism (MeSH) ; Calcium Channels: metabolism (MeSH) ; Cells, Cultured (MeSH) ; Electrophysiological Phenomena (MeSH) ; Female (MeSH) ; Gene Deletion (MeSH) ; Gene Expression (MeSH) ; Gene Targeting (MeSH) ; Genetic Loci (MeSH) ; Hippocampus: metabolism (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Knockout (MeSH) ; Neurons: metabolism (MeSH) ; Phenotype (MeSH) ; Protein Transport (MeSH) ; Synapses: metabolism (MeSH) ; Synaptic Transmission: genetics (MeSH) ; Synaptic Vesicles: metabolism (MeSH) ; Calcium Channels ; Calcium

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Contributing Institute(s):

1. Network Dysfunction (AG Schmitz 1)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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