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Am J Physiol Renal Physiol 290: F241-F250, 2006; doi:10.1152/ajprenal.00126.2005
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INVITED REVIEW

FXYD proteins: new regulators of Na-K-ATPase

Käthi Geering

Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland

FXYD proteins belong to a family of small-membrane proteins. Recent experimental evidence suggests that at least five of the seven members of this family, FXYD1 (phospholemman), FXYD2 ({gamma}-subunit of Na-K-ATPase), FXYD3 (Mat-8), FXYD4 (CHIF), and FXYD7, are auxiliary subunits of Na-K-ATPase and regulate Na-K-ATPase activity in a tissue- and isoform-specific way. These results highlight the complexity of the regulation of Na + and K + handling by Na-K-ATPase, which is necessary to ensure appropriate tissue functions such as renal Na + reabsorption, muscle contractility, and neuronal excitability. Moreover, a mutation in FXYD2 has been linked to cases of human hypomagnesemia, indicating that perturbations in the regulation of Na-K-ATPase by FXYD proteins may be critically involved in pathophysiological states. A better understanding of this novel regulatory mechanism of Na-K-ATPase should help in learning more about its role in pathophysiological states. This review summarizes the present knowledge of the role of FXYD proteins in the modulation of Na-K-ATPase as well as of other proteins, their regulation, and their structure-function relationship.

ion transport regulation; protein-protein interaction; structure-function relationship


Address for reprint requests and other correspondence: K. Geering, Dept. of Pharmacology and Toxicology, Univ. of Lausanne, Rue du Bugnon 27, 1005 Lausanne, Switzerland (e-mail: Kaethi.Geering{at}unil.ch)




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