A synaptic F-actin network controls otoferlin-dependent exocytosis in auditory inner hair cells
Philippe FY Vincent,
Yohan Bouleau,
Christine Petit,
Didier Dulon
Affiliations
Philippe FY Vincent
Bordeaux Neurocampus, Equipe Neurophysiologie de la Synapse Auditive, Université de Bordeaux, Bordeaux, France
Yohan Bouleau
Bordeaux Neurocampus, Equipe Neurophysiologie de la Synapse Auditive, Université de Bordeaux, Bordeaux, France
Christine Petit
Unité de Génétique et Physiologie de l’Audition, Institut Pasteur, Paris, France; UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France; Sorbonne Universités, UPMC Université Paris, Paris, France; Syndrome de Usher et Autres Atteintes Rétino-Cochléaires, Institut de la Vision, Paris, France; Collège de France, Paris, France
Didier Dulon
Bordeaux Neurocampus, Equipe Neurophysiologie de la Synapse Auditive, Université de Bordeaux, Bordeaux, France; UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France
We show that a cage-shaped F-actin network is essential for maintaining a tight spatial organization of Cav1.3 Ca2+ channels at the synaptic ribbons of auditory inner hair cells. This F-actin network is also found to provide mechanosensitivity to the Cav1.3 channels when varying intracellular hydrostatic pressure. Furthermore, this F-actin mesh network attached to the synaptic ribbons directly influences the efficiency of otoferlin-dependent exocytosis and its sensitivity to intracellular hydrostatic pressure, independently of its action on the Cav1.3 channels. We propose a new mechanistic model for vesicle exocytosis in auditory hair cells where the rate of vesicle recruitment to the ribbons is directly controlled by a synaptic F-actin network and changes in intracellular hydrostatic pressure.
