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Sci. STKE, 21 January 2003
Vol. 2003, Issue 166, p. re1
[DOI: 10.1126/stke.2003.166.re1]


FXYD Proteins: New Tissue-Specific Regulators of the Ubiquitous Na,K-ATPase

Gilles Crambert and Käthi Geering*

Institute of Pharmacology and Toxicology, University of Lausanne, rue du Bugnon 27, CH-Lausanne, Switzerland.

Abstract: Maintenance of the Na+ and K+ gradients between the intracellular and extracellular milieus of animal cells is a prerequisite for basic cellular homeostasis and for functions of specialized tissues. The Na,K-ATPase, an oligomeric P-type adenosine triphosphatase (ATPase), is composed of a catalytic α subunit and a regulatory β subunit and is the main player that fulfils these tasks. A variety of regulatory mechanisms are necessary to guarantee appropriate Na,K-ATPase expression and activity adapted to changing physiological demands. Recently, a regulatory mechanism was defined that is mediated by interaction of Na,K-ATPase with small proteins of the FXYD family, which possess a single transmembrane domain and so far have been considered as channels or regulators of ion channels. The mammalian FXYD proteins FXYD1 through FXYD7 exhibit tissue-specific distribution. Phospholemman (FXYD1) in heart and skeletal muscle, the {gamma} subunit of Na,K-ATPase (FXYD2) and corticosteroid hormone-induced factor (FXYD4, also known as CHIF) in the kidney, and FXYD7 in the brain associate preferentially with the widely expressed Na,K-ATPase α1-β1 isozyme and modulate its transport activity in a way that conforms to tissue-specific requirements. Thus, tissue- and isozyme-specific interaction of Na,K-ATPase with FXYD proteins contributes to proper handling of Na+ and K+ by the Na,K-ATPase, and ensures correct function in such processes as renal Na+-reabsorption, muscle contraction, and neuronal excitability.

*Corresponding author. Telephone, 41 21 692 5410; fax, 41 21 692 5355; e-mail: kaethi.geering{at}

Citation: G. Crambert, K. Geering, FXYD Proteins: New Tissue-Specific Regulators of the Ubiquitous Na,K-ATPase. Sci. STKE 2003, re1 (2003).

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