P. Vincent, D.Dulon et al. in eLife
Synaptic F-Actin Network Controls Otoferlin-Dependent Exocytosis in Auditory Inner Hair Cells.
Le 14 décembre 2015
Synaptic F-Actin Network Controls Otoferlin-Dependent Exocytosis in Auditory Inner Hair Cells. Vincent PF, Bouleau Y, Petit C, Dulon D. eLife. 2015 Nov 14;4. pii: e10988. doi: 10.7554/eLife.10988
To faithfully encode high frequency sound signals into phase-locked electrical impulses at their contacting afferent nerve fibers, auditory hair cells must be able to sustain, undefatigably, extremely high rates of exocytosis (the fusion of several hundred of synaptic vesicles per second at their presynaptic active zones). The synaptic vesicles contain the neurotransmitter glutamate. Exocytosis is triggered by Ca2+ ions entering into the hair cell presynaptic zone during the voltage-activation of L-type Ca2+ channels. One of the most important question of hearing is to understand how do hair cells can so rapidly and constantly supply their active zones with synaptic vesicles.
Main findings of the study
Here, we describe for the first time, the organization of a F-actin network that forms micrometric cages surrounding each of the presynaptic active zones of the auditory hair cells (each active zone contains one ribbon to which are attached several hundred of vesicles and a cluster of calcium channels). We show that this synaptic F-actin network controls the rate of vesicle exocytosis by both contributing to the spatial organization of the Ca2+ channels and by regulating the trafficking of the synaptic vesicles toward the presynaptic active zones. We worked on living explants of mouse organ of Corti in vitro to record, using the whole cell patch clamp technique, the exocytotic synaptic activity (fusion of synaptic vesicles to the plasma membrane of the active zones) of the auditory hair cells. We disrupted the synaptic F-actin network of the hair cells with latrunculin-A, a toxin purified from the red sea sponge Latrunculia magnifica that prevents actin repolymerization into F-actin.
Contact / Didier Dulon / DR Inserm/ Responsable d’Equipe – Neurophysiologie de la synapse auditive /
Philippe Vincent a soutenu thèse le le 16 décembre 2015 au Neurocampus/Université de Bordeaux.
Travail de thèse dans le laboratoire de Didier DULON. La thèse de Philippe Vincent a été financée par une bourse au mérite de l’Ecole Doctorale des Sciences de la Vie et de la Santé, Université de Bordeaux.