A Trio of Active Zone Proteins Comprised of RIM-BPs, RIMs, and Munc13s Governs Neurotransmitter Release.

Marisa M Brockmann, Fereshteh Zarebidaki, Marcial Camacho, M Katharina Grauel, Thorsten Trimbuch, Thomas C Südhof, Christian Rosenmund

Cell reports 2020 Aug 04

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At the presynaptic active zone, action-potential-triggered neurotransmitter release requires that fusion-competent synaptic vesicles are placed next to Ca2+ channels. The active zone resident proteins RIM, RBP, and Munc13 are essential contributors for vesicle priming and Ca2+-channel recruitment. Although the individual contributions of these scaffolds have been extensively studied, their respective functions in neurotransmission are still incompletely understood. Here, we analyze the functional interactions of RIMs, RBPs, and Munc13s at the genetic, molecular, functional, and ultrastructural levels in a mammalian synapse. We find that RBP, together with Munc13, promotes vesicle priming at the expense of RBP's role in recruiting presynaptic Ca2+ channels, suggesting that the support of RBP for vesicle priming and Ca2+-secretion coupling is mutually exclusive. Our results demonstrate that the functional interaction of RIM, RBP, and Munc13 is more profound than previously envisioned, acting as a functional trio that govern basic and short-term plasticity properties of neurotransmission. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Marisa M Brockmann, Fereshteh Zarebidaki, Marcial Camacho, M Katharina Grauel, Thorsten Trimbuch, Thomas C Südhof, Christian Rosenmund. A Trio of Active Zone Proteins Comprised of RIM-BPs, RIMs, and Munc13s Governs Neurotransmitter Release. Cell reports. 2020 Aug 04;32(5):107960