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U583

Equipe 1
Génétique et thérapie des cécités rétiniennes

Equipe 2
Physiopathologie et thérapies de l’oreille interne

Equipe 3
Neurobiologie cellulaire et moléculaire du système somato-sensoriel

Equipe 4
Physiologie et approches thérapeutiques des pathologies médullaires

Equipe 5
Physiologie et thérapie des désordres vestibulaires

U844

 

 

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Benjamin Delprat
 

Function: PhD, Senior Research Associate, Inserm
 

Research interests :

Disturbance of the ionic homeostasis is highly damageable for the cochlear function. Numerous deafness of genetic origin is due in fact to dysfunctions of the stria vascularis or a disturbance in the potassium recycling mechanisms between the hair cells and the stria vascularis. The Na,K-ATPase is a key protein in the mechanisms which maintain the endolymph electrochemical composition. The Na,K-ATPase is an ubiquitous enzyme consisting of an a and a b subunit, which is responsible for the creation and maintenance of the sodium and potassium gradients across the cell membrane. During my post doctoral period in Lausanne, I was able to demonstrate that FXYD6, strongly expressed in the stria vascularis, was a new auxiliary protein able to regulate the transport properties of Na,K-ATPase (Delprat et al., 2007). My work is dedicated to the study of potassium in the cochlea and especially on its secretion and regulation by the stria vascularis and its recycling toward the stria vascularis by the spiral ligament fibrocytes.

 

Techniques :

molecular biology (RNAi, transgenesis and homologous recombination), cellular biology (organotypic and cell culture, confocal microscopy), biochemistry (western blot, Pulse-Chase, protein-protein interaction), electrophysiology (two electrode voltage clamp).

Key words : cochlea, Na,K-ATPase, FXYD proteins, endolymph, endocochlear potential, potassium.

 

Selected publications :

 

  • Delprat B, Puel JL, Geering K. Dynamic expression of FXYD6 in the inner ear suggests a role of the protein in endolymph homeostasis and neuronal activity. Dev Dyn. 2007 Aug 5;236(9):2534-2540.

  • Delprat B, Schaer D, Roy S, Wang J, Puel JL, Geering K. FXYD6 is a novel regulator of Na,K-ATPase expressed in the inner ear. J Biol Chem. 2007 Mar 9;282(10):7450-6.

  • Delprat B, Bibert S, Geering K. Les protéines FXYDs: nouveaux régulateurs de la Na,K-ATPase. Med Sci (Paris). 2006. Jul-Aug ; 22(6-7):633-638.

  • Adato A, Lefèvre G, Delprat B, Michel V, Michalski N, Chardenoux S, Weil D, El-Amraoui A, Petit C. Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells. Human Mol. Genet. 2005. Dec 15;14(24):3921-32 ; doi:10.1093/hmg/ddi416.

  • Delprat B, Michel V, Goodyear R, Yamasaki Y, Michalski N, El-Amraoui A, Perfettini I, Legrain P, Richardson GP, Hardelin JP, Petit C. Myosin XVa and whirlin, two deafness gene products required for hair bundle growth, are located at the stereocilia tips and interact directly. Human Mol. Genet. 2005. 14: 401-410 ; Doi:10.1093/hmg/ddi036.

  • Delprat B, Ruel J, Guitton M, Hamard G, Lenoir M, Pujol R, Puel JL, Brabet P, Hamel CP. Deafness and cochlear fibrocyte alterations in mice deficient for the inner ear protein otospiralin. Mol. Cell. Biol. 2005. 25: 847-853.

  • Delprat B*,Lavigne-Rebillard M*, Surget M-O, griffoin J-M, Weil D, Arbones M, Vincent R, Hamel CP. Gene structure, chromosomal localisation and mutation screening of the human gene for the inner ear protein Otospiralin. Neurogenetics. 2003, 4(3):137-40. (*contributed equally to this work).

  • Delprat B, Boulanger A, Wang J, Beaudoin V, Guitton M, Ventéo S, Dechesne C, Lavigne-rebillard M, Puel J-L, Hamel C. Down regulation of Otospiralin, a novel inner ear protein, causes hair cell degeneration and deafness. J. Neurosci. 2002, 22 : 1718-1725.

Collaboration :

Kaethi Geering, Department of Pharmacology and Toxicology, Lausanne, Switzerland.
Evelyne Ferrary, Inserm U847, Paris, France.
Marc Lombes, Inserm U693, Paris, France.
Jean-Michel Heard, Inserm U622, Pasteur Institute, Paris, France.
Patrick Saulnier, Inserm U646, Angers, France.
 

 

 

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