1998Comparative molecular analysis of Na+-H+ exchangers— a unified model for Na+-H+ antiport.pdfVIP

FEBS 19886 FEBS Letters 424 (1998) 1^5 Minireview Comparative molecular analysis of Na?/H? exchangers: a uni￠ed model for Na?/H? antiport? Pavel Dibrov, Larry Fliegel* Department of Biochemistry, 347 Med. Sci. Bldg., University of Alberta, Edmonton, Alta. T6G 2H7, Canada Received 19 January 1998 pH of approximately 7.2. Shifts in intracellular pH initiate Abstract Despite 30 years of study on Na+/H+ exchange, the molecular mechanisms of antiport remain obscure. Most changes in the growth or functional state of the cell [5^7] ? ? challenging, the identity of amino acids involved in binding and are often initiated by the Na /H exchanger which nor- transported cations is still unknown. We review data examining mally functions to remove intracellular H? for extracellular the identity of residues that are involved in cation binding and Na? [8]. Na?/H? exchange also protects cells from intracel- translocation of prokaryotic and eukaryotic Na+/H+ antiporters. lular acidi￠cation, which is evident because mutant cell lines Several polar residues specifically distributed within or immedi- devoid of Na?/H? exchanger are highly sensitive to acidosis ately adjacent to membrane spanning regions are implicated as [9,10]. In addition, Na?/H? exchange participates in regula- being important. These key amino acids are conserved in tion of sodium ￡uxes and cell volume regulation after osmotic + prokaryotes and in some