Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers.
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.
Pang
T
T
Department of Molecular Physiology, National Cardiovascular Center Research Institute, Fujishiro-dai 5-7-1, Suita, Osaka 565-8565, Japan.
Su
X
X
Wakabayashi
S
S
Shigekawa
M
M
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D029681:Arabidopsis Proteins; D019703:Calcineurin / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D005260:Female; D017930:Genes, Reporter; D014644:Genetic Variation; D049452:Green Fluorescent Proteins; D006863:Hydrogen-Ion Concentration; D008074:Lipoproteins / Q000378:metabolism*; D008164:Luminescent Proteins / Q000032:analysis; D008565:Membrane Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection; D014982:Xenopus laevis
D029681:Arabidopsis Proteins; D019703:Calcineurin; D002135:Calcium-Binding Proteins; D049452:Green Fluorescent Proteins; D008074:Lipoproteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D012964:Sodium; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; C484078:CBL10 protein, Arabidopsis; C484079:CBL3 protein, Arabidopsis; C513110:Slc9a2 protein, rat; C000613387:Slc9a3 protein, rat; C483419:calcineurin B-like protein 1, Arabidopsis; C098929:calcium binding protein p22, rat; C069139:growth factor-activatable Na-H exchanger NHE-1; C117561:sodium-hydrogen exchanger 5; C480758:At5g55990 protein, Arabidopsis