The SNARE protein SNAP-25 is required for normal exocytosis at auditory hair cell ribbon synapses

Charlotte Calvet; Thibault Peineau; Najate Benamer; Maxence Cornille; Andrea Lelli; Baptiste Plion; Ghizlène 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

doi:10.1016/j.isci.2022.105628

The SNARE protein SNAP-25 is required for normal exocytosis at auditory hair cell ribbon synapses

iScience. 2022 Nov 22;25(12):105628. doi: 10.1016/j.isci.2022.105628. eCollection 2022 Dec 22.

Authors

Charlotte Calvet^{1

2}, Thibault Peineau³, Najate Benamer¹, Maxence Cornille¹, Andrea Lelli¹, Baptiste Plion¹, Ghizlène Lahlou^{1

2

4}, Julia Fanchette^{1

5}, Sylvie Nouaille¹, Jacques Boutet de Monvel¹, Amrit Estivalet¹, Philippe Jean¹, Vincent Michel¹, Martin Sachse⁶, Nicolas Michalski¹, Paul Avan⁷, Christine Petit¹, Didier Dulon^{1

3}, Saaid Safieddine^{1

2

8}

Affiliations

¹ Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France.
² Sorbonne Université, Collège doctoral, 75005 Paris, France.
³ Bordeaux NeuroCampus, Université de Bordeaux, 33076 Bordeaux, France.
⁴ APHP, Sorbonne Université, Service d'ORL et de chirurgie cervico-faciale, 75013 Paris, France.
⁵ APHP, Service d'ORL et de chirurgie cervico-faciale, Hôpital Bichat - Claude-Bernard, 75018 Paris, France.
⁶ UTechS Ultrastructural Bio Imaging, Institut Pasteur, Université de Paris, 75015 Paris, France.
⁷ Laboratoire de Biophysique Sensorielle, Faculté́ de Médecine, Université́; d'Auvergne, Biophysique Médicale, Centre Jean Perrin, 63000 Clermont-Ferrand, France.
⁸ Centre National de la Recherche Scientifique, France.

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 Snap-25 in IHCs. Mice subjected to IHC Snap-25 inactivation after hearing onset developed severe to profound deafness because of defective IHC exocytosis followed by ribbon degeneration and IHC loss. Viral transfer of Snap-25 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.

Keywords: Biological sciences; Neuroscience; Sensory neuroscience.