CHIF, a member of the FXYD protein family, is a regulator of Na,K-ATPase distinct from the gamma-subunit.
The biological role of small membrane proteins of the new FXYD family is largely unknown. The best characterized FXYD protein is the gamma-subunit of the Na,K-ATPase (NKA) that modulates the Na,K-pump function in the kidney. Here, we report that, similarly to gamma(a) and gamma(b) 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 gamma(a) and gamma(b), 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 gamma-subunit and CHIF interaction with NKA, while cytoplasmic, positively charged residues are necessary for the gamma-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.
Béguin
P
P
Institut de Pharmacologie et de Toxicologie de l'Université de Lausanne, Rue du Bugnon 27, CH-1005 Lausanne, Switzerland.
Crambert
G
G
Guennoun
S
S
Garty
H
H
Horisberger
J D
JD
Geering
K
K
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D007527:Isoenzymes; D008565:Membrane Proteins; C422209:corticosteroid hormone-induced factor; C416502:FXYD2 protein, human; C498817:Fxyd2 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase