Physiological role and regulation of the Na+/H+ exchanger.
In mammalian eukaryotic cells, the Na+/H+ exchanger is a family of membrane proteins that regulates ions fluxes across membranes. Plasma membrane isoforms of this protein extrude 1 intracellular proton in exchange for 1 extracellular sodium. The family of Na+/H+ exchangers (NHEs) consists of 9 known isoforms, NHE1-NHE9. The NHE1 isoform was the first discovered, is the best characterized, and exists on the plasma membrane of all mammalian cells. It contains an N-terminal 500 amino acid membrane domain that transports ions, plus a 315 amino acid C-terminal, the intracellular regulatory domain. The Na+/H+ exchanger is regulated by both post-translational modifications including protein kinase-mediated phosphorylation, plus by a number of regulatory-binding proteins including phosphatidylinositol-4,5-bisphosphate, calcineurin homologous protein, ezrin, radixin and moesin, calmodulin, carbonic anhydrase II, and tescalcin. The Na+/H+ exchanger is involved in a variety of complex physiological and pathological events that include regulation of intracellular pH, cell movement, heart disease, and cancer. This review summarizes recent advances in the understanding of the physiological role and regulation of this protein.
Malo
Mackenzie E
ME
Department of Biochemistry, 347 Medical Science Building, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Fliegel
Larry
L
D000494:Allosteric Regulation; D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D004789:Enzyme Activation; D006331:Heart Diseases / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008968:Molecular Conformation; D009369:Neoplasms / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000378:metabolism*
D027682:Cation Transport Proteins; D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers