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

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Abstract
Like the γ-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 γ, γaand γb, are expressed in the kidney. Immunolocalization experiments demonstrate mutually exclusive expression of CHIF and γ in different nephron segments. Specific coimmunoprecipitation experiments demonstrate the existence in kidney membranes of the complexes α/β/γa, α/β/γb, and α/β/CHIF and exclude mixed complexes such as α/β/γa/γband α/β/γ/CHIF. CHIF has been expressed in HeLa cells harboring the rat α1-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′Kand K′ATPare unaffected. The functional effects of CHIF differ from those of γ. An implication of these findings is that other FXYD proteins could act as tissue-specific modulators of Na-K-ATPase.