Abstract
The Na+/H+ exchangers (NHEs) comprise a family of transporters that catalyze cell functions such as regulation of the pH and volume of a cell and epithelial absorption of Na+ and bicarbonate. Ubiquitous calcineurin B homologous protein (CHP or p22) is co-localized and co-immunoprecipitated with expressed NHE1, NHE2, or NHE3 independently of its myristoylation and Ca2+ binding, and its binding site was identified as the juxtamembrane region within the carboxyl-terminal cytoplasmic domain of exchangers. CHP binding-defective mutations of NHE1-3 or CHP depletion by injection of the competitive CHP-binding region of NHE1 into Xenopus oocytes resulted in a dramatic reduction (>90%) in the Na+/H+ exchange activity. The data suggest that CHP serves as an essential cofactor, which supports the physiological activity of NHE family members.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Animals
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Arabidopsis Proteins*
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Calcineurin / metabolism*
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Calcium-Binding Proteins / metabolism*
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Female
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Genes, Reporter
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Genetic Variation
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Green Fluorescent Proteins
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Hydrogen-Ion Concentration
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Lipoproteins / metabolism*
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Luminescent Proteins / analysis
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Membrane Proteins
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Oocytes / physiology
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Protein Conformation
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Recombinant Proteins / metabolism
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Sodium / metabolism
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Sodium-Hydrogen Exchanger 3
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Sodium-Hydrogen Exchangers / chemistry
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Sodium-Hydrogen Exchangers / metabolism*
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Transfection
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Xenopus laevis
Substances
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Arabidopsis Proteins
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CBL10 protein, Arabidopsis
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CBL3 protein, Arabidopsis
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CLB2 protein, Arabidopsis
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Calcium-Binding Proteins
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Lipoproteins
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Luminescent Proteins
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Membrane Proteins
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Recombinant Proteins
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Slc9a2 protein, rat
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Slc9a3 protein, rat
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Sodium-Hydrogen Exchanger 3
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Sodium-Hydrogen Exchangers
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calcineurin B-like protein 1, Arabidopsis
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calcium binding protein p22, rat
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growth factor-activatable Na-H exchanger NHE-1
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sodium-hydrogen exchanger 5
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Green Fluorescent Proteins
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Sodium
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Calcineurin