Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers

J Biol Chem. 2001 May 18;276(20):17367-72. doi: 10.1074/jbc.M100296200. Epub 2001 Feb 28.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Arabidopsis Proteins*
  • Calcineurin / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Female
  • Genes, Reporter
  • Genetic Variation
  • Green Fluorescent Proteins
  • Hydrogen-Ion Concentration
  • Lipoproteins / metabolism*
  • Luminescent Proteins / analysis
  • Membrane Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oocytes / physiology
  • Protein Conformation
  • Recombinant Proteins / metabolism
  • Sodium / metabolism
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers / chemistry
  • Sodium-Hydrogen Exchangers / metabolism*
  • Transfection
  • Xenopus laevis

Substances

  • Arabidopsis Proteins
  • CBL10 protein, Arabidopsis
  • CBL3 protein, Arabidopsis
  • CLB2 protein, Arabidopsis
  • Calcium-Binding Proteins
  • Lipoproteins
  • Luminescent Proteins
  • Membrane Proteins
  • Recombinant Proteins
  • Slc9a2 protein, rat
  • Slc9a3 protein, rat
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers
  • calcineurin B-like protein 1, Arabidopsis
  • calcium binding protein p22, rat
  • growth factor-activatable Na-H exchanger NHE-1
  • sodium-hydrogen exchanger 5
  • Green Fluorescent Proteins
  • Sodium
  • Calcineurin