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Originally published In Press as doi:10.1074/jbc.M609872200 on January 5, 2007

J. Biol. Chem., Vol. 282, Issue 10, 7450-7456, March 9, 2007
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FXYD6 Is a Novel Regulator of Na,K-ATPase Expressed in the Inner Ear*

Benjamin Delprat{ddagger}, Danièle Schaer{ddagger}, Sophie Roy{ddagger}, Jing Wang§, Jean-Luc Puel§, and Käthi Geering{ddagger}1

From the {ddagger}Department of Pharmacology and Toxicology, University of Lausanne, Rue du Bugnon 27, 1005 Lausanne, Switzerland and §Institut National de la Santé et de la Recherche Médicale U583, Institut des Neurosciences de Montpellier and University of Montpellier 1, 34091 Montpellier, France

The exquisite sensitivity of the cochlea, which mediates the transduction of sound waves into nerve impulses, depends on the endolymph ionic composition and the endocochlear potential. A key protein in the maintenance of the electrochemical composition of the endolymph is the Na,K-ATPase. In this study, we have looked for the presence in the rat inner ear of members of the FXYD protein family, recently identified as tissue-specific modulators of Na,K-ATPase. Only FXYD6 is detected at the protein level. FXYD6 is expressed in various epithelial cells bordering the endolymph space and in the auditory neurons. FXYD6 co-localizes with Na,K-ATPase in the stria vascularis and can be co-immunoprecipitated with Na,K-ATPase. After expression in Xenopus oocytes, FXYD6 associates with Na,K-ATPase {alpha}1-beta1 and {alpha}1-beta2 isozymes, which are preferentially expressed in different regions of the inner ear and also with gastric and non-gastric H,K-ATPases. The apparent K+ and Na+ affinities of {alpha}1-beta1 and {alpha}1-beta2 isozymes are different. Association of FXYD6 with Na,K-ATPase {alpha}1-beta1 isozymes slightly decreases their apparent K+ affinity and significantly decreases their apparent Na+ affinity. On the other hand, association with {alpha}1-beta2 isozymes increases their apparent K+ and Na+ affinity. The effects of FXYD6 on the apparent Na+ affinity of Na,K-ATPase and the voltage dependence of its K+ effect are distinct from other FXYD proteins. In conclusion, this study defines the last FXYD protein of unknown function as a modulator of Na,K-ATPase. Among FXYD protein, FXYD6 is unique in its expression in the inner ear, suggesting a role in endolymph composition.


Received for publication, October 20, 2006 , and in revised form, December 21, 2006.

* This study was supported by Grant 3100A0-107513 (to K. G.) from the Swiss National Science Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: Department of Pharmacology and Toxicology, University of Lausanne, Rue du Bugnon 27, 1005 Lausanne, Switzerland. Tel.: 41-21-692-54-10; Fax: 41-21-692-53-55; E-mail: Kaethi.Geering{at}unil.ch.


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