Heterodimerization of Munc13 CA Domain with RIM Regulates Synaptic Vesicle Docking and Priming

Overview

Journal Nat Commun

Specialty Biology

Date 2017 May 11

PMID 28489077

Citations 54

Authors

Marcial Camacho

Jayeeta Basu

Thorsten Trimbuch

Shuwen Chang

Cristina Pulido-Lozano

Shwu-Shin Chang

Irina Duluvova

Masin Abo-Rady

Josep Rizo

Christian Rosenmund

Affiliations

Soon will be listed here.

Abstract

The presynaptic active zone protein Munc13 is essential for neurotransmitter release, playing key roles in vesicle docking and priming. Mechanistically, it is thought that the CA domain of Munc13 inhibits the priming function by homodimerization, and that RIM disrupts the autoinhibitory homodimerization forming monomeric priming-competent Munc13. However, it is unclear whether the CA domain mediates other Munc13 functions in addition to this inactivation-activation switch. Here, we utilize mutations that modulate the homodimerization and heterodimerization states to define additional roles of the Munc13 CA domain. Using electron microscopy and electrophysiology in hippocampal cultures, we show that the CA domain is critical for additional steps of vesicular release, including vesicle docking. Optimal vesicle docking and priming is only possible when Munc13 heterodimerizes with RIM via its CA domain. Beyond being a switching module, our data suggest that the Munc13-RIM heterodimer is an active component of the vesicle docking, priming and release complex.

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