title: FXYD6 is a novel regulator of Na,K-ATPase expressed in the inner ear.
abstract: 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 alpha1-beta1 and alpha1-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 alpha1-beta1 and alpha1-beta2 isozymes are different. Association of FXYD6 with Na,K-ATPase alpha1-beta1 isozymes slightly decreases their apparent K(+) affinity and significantly decreases their apparent Na(+) affinity. On the other hand, association with alpha1-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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Lausanne, Rue du Bugnon 27, 1005 Lausanne, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Delprat
authors.forename: Danièle
authors.initials: D
authors.lastname: Schaer
authors.forename: Sophie
authors.initials: S
authors.lastname: Roy
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Puel
authors.forename: Käthi
authors.initials: K
authors.lastname: Geering
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003051:Cochlea / Q000737:chemistry; D007758:Ear, Inner / Q000201:enzymology*; D004710:Endolymph / Q000737:chemistry; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D007473:Ion Channels / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016716:PC12 Cells; D011188:Potassium / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013316:Stria Vascularis / Q000737:chemistry; D014981:Xenopus
chemical_list: C518765:FXYD6 protein, mouse; D007473:Ion Channels; D012964:Sodium; D017506:H(+)-K(+)-Exchanging ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium