Synaptic F-actin network controls otoferlin-dependent exocytosis in auditory inner hair cells

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Abstract

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.

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Philippe FY Vincent

Bordeaux Neurocampus, Equipe Neurophysiologie de la Synapse Auditive, Centre Hospitalier Universitaire de Bordeaux, Université de Bordeaux, Bordeaux, France

Competing interests
The authors declare that no competing interests exist.
Yohan Bouleau

Bordeaux Neurocampus, Equipe Neurophysiologie de la Synapse Auditive, Centre Hospitalier Universitaire de Bordeaux, Université de Bordeaux, Bordeaux, France

Competing interests
The authors declare that no competing interests exist.
Christine Petit

Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, Paris, France

Competing interests
The authors declare that no competing interests exist.
Didier Dulon

Bordeaux Neurocampus, Equipe Neurophysiologie de la Synapse Auditive, Centre Hospitalier Universitaire de Bordeaux, Université de Bordeaux, Bordeaux, France

For correspondence
didier.dulon@inserm.fr

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in accordance with the guidelines of the Animal Care Committee of the European Communities Council Directive (86/609/EEC) and were approved by the ethics committee of the University of Bordeaux (animal facility agreement 155 number C33-063-075)

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.