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

Standard

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

In: P NATL ACAD SCI USA, Vol. 113, No. 41, 11.10.2016, p. 11615-11620.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Grauel, MK, Maglione, M, Reddy-Alla, S, Willmes, CG, Brockmann, MM, Trimbuch, T, Rosenmund, T, Pangalos, M, Vardar, G, Stumpf, A, Walter, AM, Rost, BR, Eickholt, BJ, Haucke, V, Schmitz, D, Sigrist, SJ & Rosenmund, C 2016, 'RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses', P NATL ACAD SCI USA, vol. 113, no. 41, pp. 11615-11620. https://doi.org/10.1073/pnas.1605256113

APA

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., & Rosenmund, C. (2016). RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses. P NATL ACAD SCI USA, 113(41), 11615-11620. https://doi.org/10.1073/pnas.1605256113

Vancouver

Grauel MK, Maglione M, Reddy-Alla S, Willmes CG, Brockmann MM, Trimbuch T et al. RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses. P NATL ACAD SCI USA. 2016 Oct 11;113(41):11615-11620. https://doi.org/10.1073/pnas.1605256113

Bibtex

@article{fc9cf02cd7734ad0adc826b51627f8eb,
title = "RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses",
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.",
keywords = "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",
author = "Grauel, {M Katharina} and Marta Maglione and Suneel Reddy-Alla and Willmes, {Claudia G} and Brockmann, {Marisa M} and Thorsten Trimbuch and Tanja Rosenmund and Maria Pangalos and G{\"u}l{\c c}in Vardar and Alexander Stumpf and Walter, {Alexander M} and Rost, {Benjamin R} and Eickholt, {Britta J} and Volker Haucke and Dietmar Schmitz and Sigrist, {Stephan J} and Christian Rosenmund",
year = "2016",
month = oct,
day = "11",
doi = "10.1073/pnas.1605256113",
language = "English",
volume = "113",
pages = "11615--11620",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "41",

}

RIS

TY - JOUR

T1 - RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses

AU - Grauel, M Katharina

AU - Maglione, Marta

AU - Reddy-Alla, Suneel

AU - Willmes, Claudia G

AU - Brockmann, Marisa M

AU - Trimbuch, Thorsten

AU - Rosenmund, Tanja

AU - Pangalos, Maria

AU - Vardar, Gülçin

AU - Stumpf, Alexander

AU - Walter, Alexander M

AU - Rost, Benjamin R

AU - Eickholt, Britta J

AU - Haucke, Volker

AU - Schmitz, Dietmar

AU - Sigrist, Stephan J

AU - Rosenmund, Christian

PY - 2016/10/11

Y1 - 2016/10/11

N2 - 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.

AB - 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.

KW - Action Potentials

KW - Animals

KW - Calcium/metabolism

KW - Calcium Channels/metabolism

KW - Cells, Cultured

KW - Electrophysiological Phenomena

KW - Female

KW - Gene Deletion

KW - Gene Expression

KW - Gene Targeting

KW - Genetic Loci

KW - Hippocampus/metabolism

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Neurons/metabolism

KW - Phenotype

KW - Protein Transport

KW - Synapses/metabolism

KW - Synaptic Transmission/genetics

KW - Synaptic Vesicles/metabolism

U2 - 10.1073/pnas.1605256113

DO - 10.1073/pnas.1605256113

M3 - SCORING: Journal article

C2 - 27671655

VL - 113

SP - 11615

EP - 11620

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 41

ER -