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

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, γa and 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/γb and 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) orV max. Measurements of Na-K-ATPase using isolated membranes show similar but smaller effects of CHIF onK′Na, whereasK′K andK′ATP are unaffected. The functional effects of CHIF differ from those...