FXYD proteins: new regulators of Na-K-ATPase.
FXYD proteins belong to a family of small-membrane proteins. Recent experimental evidence suggests that at least five of the seven members of this family, FXYD1 (phospholemman), FXYD2 (gamma-subunit of Na-K-ATPase), FXYD3 (Mat-8), FXYD4 (CHIF), and FXYD7, are auxiliary subunits of Na-K-ATPase and regulate Na-K-ATPase activity in a tissue- and isoform-specific way. These results highlight the complexity of the regulation of Na+ and K+ handling by Na-K-ATPase, which is necessary to ensure appropriate tissue functions such as renal Na+ reabsorption, muscle contractility, and neuronal excitability. Moreover, a mutation in FXYD2 has been linked to cases of human hypomagnesemia, indicating that perturbations in the regulation of Na-K-ATPase by FXYD proteins may be critically involved in pathophysiological states. A better understanding of this novel regulatory mechanism of Na-K-ATPase should help in learning more about its role in pathophysiological states. This review summarizes the present knowledge of the role of FXYD proteins in the modulation of Na-K-ATPase as well as of other proteins, their regulation, and their structure-function relationship.
Geering
Käthi
K
Dept. of Pharmacology and Toxicology, Univ. of Lausanne, Rue du Bugnon 27, 1005 Lausanne, Switzerland. Kaethi.Geering@unil.ch
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D008969:Molecular Sequence Data; D009399:Nephrons / Q000378:metabolism; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000502:physiology*; D013329:Structure-Activity Relationship
D008565:Membrane Proteins; D021122:Protein Subunits; D000254:Sodium-Potassium-Exchanging ATPase