SUMMARY: The NHAl gene of Saccharomyces cerevisiae, transcribed into a 3-5 kb mRNA, encodes a protein mediating Na+ and K+ efflux through the plasma membrane that is required for alkali cation tolerance at acidic pH. Deletion of the gene in a wild-type strain resulted in higher sensitivity to both K+ and Na+ at acidic pH. Measurements of cation loss in strains carrying deleted or overexpressed alleles of NHAl demonstrated its role in K+ and Na+ efflux. In addition, high K+ and Na+ efflux observed upon alkalinization of the cytoplasm implies a role of Nhalp in the regulation of intracellular pH. Moreover, the overexpression of ENA1 and NHAl genes in an enal-46-nhalb strain showed that the Nhal alkalication antiporter is responsible for growth on high concentrations of KCI and NaCl at acidic pH, and Ena alkali-cation ATPases are necessary at higher pH values. Both systems have a complementary action to maintain the intracellular steadystate concentration of K+ and Na+.


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