Calcium-dependent neurotransmitter release at the ribbon synapse of auditory and vestibular hair cells: what role for otoferlin?
- Name : Didier Dulon
Mutations of the otoferlin gene underlie the non-syndromic prelingual deafness disorder DFNB9. This genetic disorder has been recently demonstrated to originate from a synaptic deficit at the inner hair cell synapse. Indeed mice presenting a null mutation for otoferlin are deaf and show cochlear inner hair cells (IHCs) lacking in calcium-evoked exocytosis of neurotransmitter.
The goal of the present project is to progress in understanding otoferlin function. We think that a detailed structural and biochemical characterization of otoferlin activities will give interesting insights for the understanding of the molecular mechanisms underlying the high temporal precision and endless property of neurotransmitter release at the IHC ribbon synapses.
An other important open question is the role played by otoferlin in other ribbon synapses of the inner ear, namely vestibular hair cells (VHCs) of type I and II, and cochlear outer hair cells (OHCs), where otoferlin is also highly expressed. By monitoring the change in membrane capacitance, we aim to characterize synaptic vesicle exocytosis in OHCs and VHCs of otoferlin knock-out mice. We will compare the calcium and otoferlin dependency of VHCs and OHCs with those analyzed in IHCs.
The overall aim of this project is to better understand the molecular mechanisms of synaptic neurotransmission at the sensory auditory and vestibular hair cells. This research will certainly help in a near future to define therapeutic gene transfer strategies that address genetic defects of neurotransmission in the inner ear.
- Dulon D, Safieddine S, Jones SM, Petit C. Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses. J Neurosci. 2009 Aug 26;29(34):10474-87.
- Beurg M, Michalski N, Safieddine S, Bouleau Y, Schneggenburger R, Chapman ER, Petit C, Dulon D. Control of exocytosis by synaptotagmins and otoferlin in auditory hair cells. J Neurosci. 2010 Oct 6;30(40):13281-90.
Rare disease day 2017
The Rare Disease Day - held on the last day of February since its first celebration in 2008 - serves to raise and deepen awareness of rare diseases among the general public, public authorities and decision-makers.Read more
Opening of the Hearing Institute - Group leader positions
The Hearing Institute, an auditory neuroscience research institute, will open in April 2018. Various funding opportunities are available. Both senior and junior group leader applications will be considered.Read more
En partenariat avec l'Institut de la Vision, le congrès Vision-Innovation© se déroulera le 10 février 2015 à la Maison de l'UNESCO.