FXYD7 is a brain-specific regulator of Na,K-ATPase alpha 1-beta isozymes.
Recently, corticosteroid hormone-induced factor (CHIF) and the gamma-subunit, two members of the FXYD family of small proteins, have been identified as regulators of renal Na,K-ATPase. In this study, we have investigated the tissue distribution and the structural and functional properties of FXYD7, another family member which has not yet been characterized. Expressed exclusively in the brain, FXYD7 is a type I membrane protein bearing N-terminal, post-translationally added modifications on threonine residues, most probably O-glycosylations that are important for protein stabilization. Expressed in Xenopus oocytes, FXYD7 can interact with Na,K-ATPase alpha 1-beta 1, alpha 2-beta 1 and alpha 3-beta 1 but not with alpha-beta 2 isozymes, whereas, in brain, it is only associated with alpha 1-beta isozymes. FXYD7 decreases the apparent K(+) affinity of alpha 1-beta 1 and alpha 2-beta 1, but not of alpha 3-beta1 isozymes. These data suggest that FXYD7 is a novel, tissue- and isoform-specific Na,K-ATPase regulator which could play an important role in neuronal excitability.
Béguin
Pascal
P
Institute of Pharmacology and Toxicology, University of Lausanne, rue du Bugnon 27, CH-1005 Lausanne, Switzerland.
Crambert
Gilles
G
Monnet-Tschudi
Florianne
F
Uldry
Marc
M
Horisberger
Jean-Daniel
JD
Garty
Haim
H
Geering
Käthi
K
D000200:Action Potentials; D000818:Animals; D001923:Brain Chemistry; D020126:Brefeldin A / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D006031:Glycosylation; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes; D009928:Organ Specificity; D011188:Potassium / Q000378:metabolism; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
D018076:DNA, Complementary; C462940:Fxyd7 protein, mouse; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D020126:Brefeldin A; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium