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CHIF, a member of the FXYD protein family, is a regulator of Na,K-ATPase distinct from the γ-subunit

By Pascal Béguin, Gilles Crambert, Saida Guennoun, Haim Garty, Jean-Daniel Horisberger and Käthi Geering


The biological role of small membrane proteins of the new FXYD family is largely unknown. The best characterized FXYD protein is the γ-subunit of the Na,K-ATPase (NKA) that modulates the Na,K-pump function in the kidney. Here, we report that, similarly to γa and γb splice variants, the FXYD protein CHIF (corticosteroid-induced factor) is a type I membrane protein which is associated with NKA in renal tissue, and modulates the Na,K-pump transport when expressed in Xenopus oocytes. In contrast to γa and γb, which both decrease the apparent Na(+) affinity of the Na,K-pump, CHIF significantly increases the Na(+) affinity and decreases the apparent K(+) affinity due to an increased Na(+) competition at external binding sites. The extracytoplasmic FXYD motif is required for stable γ-subunit and CHIF interaction with NKA, while cytoplasmic, positively charged residues are necessary for the γ-subunit’s association efficiency and for CHIF’s functional effects. These data document that CHIF is a new tissue-specific regulator of NKA which probably plays a crucial role in aldosterone-responsive tissues responsible for the maintenance of body Na(+) and K(+) homeostasis

Topics: Article
Publisher: Oxford University Press
Year: 2001
DOI identifier: 10.1093/emboj/20.15.3993
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Provided by: PubMed Central
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