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
Affiliations
Charlotte Calvet
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France; Sorbonne Université, Collège doctoral, 75005 Paris, France
Thibault Peineau
Bordeaux NeuroCampus, Université de Bordeaux, 33076 Bordeaux, France
Najate Benamer
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Maxence Cornille
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Andrea Lelli
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Baptiste Plion
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Ghizlène Lahlou
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France; Sorbonne Université, Collège doctoral, 75005 Paris, France; APHP, Sorbonne Université, Service d’ORL et de chirurgie cervico-faciale, 75013 Paris, France
Julia Fanchette
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France; APHP, Service d’ORL et de chirurgie cervico-faciale, Hôpital Bichat - Claude-Bernard, 75018 Paris, France
Sylvie Nouaille
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Jacques Boutet de Monvel
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Amrit Estivalet
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Philippe Jean
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Vincent Michel
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Martin Sachse
UTechS Ultrastructural Bio Imaging, Institut Pasteur, Université de Paris, 75015 Paris, France
Nicolas Michalski
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Paul Avan
Laboratoire de Biophysique Sensorielle, Faculté́ de Médecine, Université́; d’Auvergne, Biophysique Médicale, Centre Jean Perrin, 63000 Clermont-Ferrand, France
Christine Petit
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France
Didier Dulon
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France; Bordeaux NeuroCampus, Université de Bordeaux, 33076 Bordeaux, France
Saaid Safieddine
Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, 75012 Paris, France; Sorbonne Université, Collège doctoral, 75005 Paris, France; Centre National de la Recherche Scientifique, France; Corresponding author
Summary: 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.
