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21 (13): 3264-3273

Copyright © 2002 by the European Molecular Biology Organization.

FXYD7 is a brain-specific regulator of Na,K-ATPase {alpha}1–ß isozymes

Pascal Béguin, Gilles Crambert, Florianne Monnet-Tschudi1, Marc Uldry, Jean-Daniel Horisberger, Haim Garty2, and Käthi Geering3

Institute of Pharmacology and Toxicology and 1 Institute of Physiology, University of Lausanne, rue du Bugnon 27, CH-1005 Lausanne, Switzerland and 2 Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100 Israel 3 Corresponding author e-mail: kaethi.geering{at}ipharm.unil.chP.Béguin and G.Crambert contributed equally to this work

Abstract: Recently, corticosteroid hormone-induced factor (CHIF) and the {gamma}-subunit, two members of the FXYD family of small proteins, have been identified as regulators of renal Na,K-ATPase. In this study, we have investigated the tissue distribution and the structural and functional properties of FXYD7, another family member which has not yet been characterized. Expressed exclusively in the brain, FXYD7 is a type I membrane protein bearing N-terminal, post-translationally added modifications on threonine residues, most probably O-glycosylations that are important for protein stabilization. Expressed in Xenopus oocytes, FXYD7 can interact with Na,K-ATPase {alpha}1–ß1, {alpha}2–ß1 and {alpha}3–ß1 but not with {alpha}–ß2 isozymes, whereas, in brain, it is only associated with {alpha}1–ß isozymes. FXYD7 decreases the apparent K+ affinity of {alpha}1–ß1 and {alpha}2–ß1, but not of {alpha}3–ß1 isozymes. These data suggest that FXYD7 is a novel, tissue- and isoform-specific Na,K-ATPase regulator which could play an important role in neuronal excitability.

Key Words: Keywords: brain Na,K-ATPase modulator/FXYD7/FXYD proteins/Xenopus oocytes

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Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882