Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials
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Animals
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Brain Chemistry*
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Brefeldin A / pharmacology
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DNA, Complementary / genetics
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Glycosylation
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Isoenzymes / metabolism*
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Kidney / metabolism
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Microsomes / metabolism
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Mutagenesis, Site-Directed
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology*
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Neurons / metabolism*
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Oocytes
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Organ Specificity
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Potassium / metabolism
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Protein Interaction Mapping
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Protein Processing, Post-Translational
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Protein Subunits
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RNA, Messenger / analysis
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Rats
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Recombinant Fusion Proteins / physiology
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Sodium-Potassium-Exchanging ATPase / genetics
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Sodium-Potassium-Exchanging ATPase / metabolism*
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Structure-Activity Relationship
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Xenopus laevis
Substances
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DNA, Complementary
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Fxyd7 protein, mouse
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Isoenzymes
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Membrane Glycoproteins
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Nerve Tissue Proteins
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Protein Subunits
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RNA, Messenger
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Recombinant Fusion Proteins
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Brefeldin A
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Sodium-Potassium-Exchanging ATPase
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Potassium