The SNARE Protein SNAP-25 is Required for Normal Exocytosis at Auditory Hair Cell Ribbon Synapses

Overview

Journal iScience

Publisher Cell Press

Date 2022 Dec 9

PMID 36483015

Authors

Charlotte Calvet

Thibault Peineau

Najate Benamer

Maxence Cornille

Andrea Lelli

Baptiste Plion

Ghizlene Lahlou

Julia Fanchette

Sylvie Nouaille

Jacques Boutet de Monvel

Amrit Estivalet

Philippe Jean

Vincent Michel

Martin Sachse

Nicolas Michalski

Paul Avan

Christine Petit

Didier Dulon

Saaid Safieddine

Affiliations

Soon will be listed here.

Abstract

Hearing depends on fast and sustained calcium-dependent synaptic vesicle fusion at the ribbon synapses of cochlear inner hair cells (IHCs). The implication of the canonical neuronal SNARE complex in this exocytotic process has so far remained controversial. We investigated the role of SNAP-25, a key component of this complex, in hearing, by generating and analyzing a conditional knockout mouse model allowing a targeted postnatal deletion of in IHCs. Mice subjected to IHC inactivation after hearing onset developed severe to profound deafness because of defective IHC exocytosis followed by ribbon degeneration and IHC loss. Viral transfer of in these mutant mice rescued their hearing function by restoring IHC exocytosis and preventing synapses and hair cells from degeneration. These results demonstrate that SNAP-25 is essential for normal hearing function, most likely by ensuring IHC exocytosis and ribbon synapse maintenance.

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