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

Charlotte Calvet (1, 2) , Thibault Peineau (3, 4) , Najate Benamer (1) , Maxence Cornille (1) , Andrea Lelli (1) , Baptiste Plion (1) , Ghizlène Lahlou (1, 2, 5) , Julia Fanchette (1, 6) , Sylvie Nouaille (1) , Jacques Boutet de Monvel (1) , Amrit Estivalet (1) , Philippe Jean (1) , Vincent Michel (1) , Martin Sachse (7) , Nicolas Michalski (1) , Paul Avan (8, 9) , Christine Petit (1) , Didier Dulon (1, 3, 4) , Saaid Safieddine (1, 2)

1 IDA - Institut de l'Audition [Paris]
2 Collège Doctoral
3 UB - Université de Bordeaux
4 CBNA - Centre Broca Nouvelle Aquitaine [Neurocampus Bordeaux]
5 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
6 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
7 UTechS UBI - Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform
8 Laboratoire de Biophysique sensorielle
9 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]

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.

Mots clés: Biological sciences; Neuroscience; Sensory neuroscience; Biological sciences

Domaines: Sciences du Vivant [q-bio]

Charlotte Calvet, Thibault Peineau, Najate Benamer, Maxence Cornille, Andrea Lelli, et al.. The SNARE protein SNAP-25 is required for normal exocytosis at auditory hair cell ribbon synapses. iScience, 2022, 25 (12), pp.105628. ⟨10.1016/j.isci.2022.105628⟩. ⟨pasteur-03985560⟩