Na⁺/H⁺ antiporters, molecular devices that couple the Na⁺ and H⁺ circulation in cells

Na⁺/H⁺ antiporters are universal devices involved in the Na⁺ and H⁺ circulation of both eukaroyotes and prokaryotes, thus playing an essential role in the pH and Na⁺ homeostasis of cells. This review focuses on the major impact of the application of molecular biology tools in the study of the antiporters. These tools permit the verification of the role of the antiporters and provide insights into their unique biology. A novel signal transduction to Na⁺ involving nhaR, a positive regulator, controls the expression of nhaA in E. coli. A "pH sensor" regulates the activity of Na⁺/H⁺ antiporters, both in eukaryotes and prokaryotes. A most intricate signal transduction to pH involving phosphorylation steps controls the activity of nhel in higher mammals. The identification of Histidine 226 in the "pH sensor" of NhaA is a step forward towards the understanding of the pH regulation of these proteins.