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Am J Physiol Renal Physiol 283: F607-F615, 2002. First published April 16, 2002; doi:10.1152/ajprenal.00112.2002
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Vol. 283, Issue 4, F607-F615, October 2002

A functional interaction between CHIF and Na-K-ATPase: implication for regulation by FXYD proteins

Haim Garty1, Moshit Lindzen1, Rosemarie Scanzano2, Roman Aizman1, Maria Füzesi1, Rivka Goldshleger1, Nicolette Farman3, Rhoda Blostein2, and Steven J. D. Karlish1

1 Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel; 3 Institut National de la Santé et de la Recherche Médicale U-478, Institut Federatif de Recherche 02, Faculte de Medecine X. Bichat, 75870 Paris Cedex 18, France; and 2 Department of Medicine, McGill University, Montreal, Quebec, Canada H3G1A4

Like the gamma -subunit of Na-K-ATPase, the corticosteroid hormone-induced factor (CHIF) is a member of the FXYD family of one-transmembrane-segment proteins. Both CHIF and two splice variants of gamma , gamma a and gamma b, are expressed in the kidney. Immunolocalization experiments demonstrate mutually exclusive expression of CHIF and gamma  in different nephron segments. Specific coimmunoprecipitation experiments demonstrate the existence in kidney membranes of the complexes alpha /beta /gamma a, alpha /beta /gamma b, and alpha /beta /CHIF and exclude mixed complexes such as alpha /beta /gamma a/gamma b and alpha /beta /gamma /CHIF. CHIF has been expressed in HeLa cells harboring the rat alpha 1-subunit of Na-K-ATPase. 86Rb flux experiments demonstrate that CHIF induces a two- to threefold increase in apparent affinity for cytoplasmic Na (K'Na) but does not affect affinity for extracellular K (Rb) ions (K'K) or Vmax. Measurements of Na-K-ATPase using isolated membranes show similar but smaller effects of CHIF on K'Na, whereas K'K and K'ATP are unaffected. The functional effects of CHIF differ from those of gamma . An implication of these findings is that other FXYD proteins could act as tissue-specific modulators of Na-K-ATPase.

corticosteroid hormone-induced factor; sodium-potassium-adenosine 5'-triphosphatase; tissue-specific modulator


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