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Calcium-dependent neurotransmitter release at the ribbon synapse of auditory and vestibular hair cells: what role for otoferlin?


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  • Name : Didier Dulon
  • E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Presentation

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.

Publications

  • 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.
Created Wednesday, 16 June 2010 Last modified Wednesday, 31 August 2011

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