| Title: | Ion tolerance of Saccharomyces cerevisiae lacking the Ca2+/CaM-dependent phosphatase (calcineurin) is improved by mutations in URE2 or PMA1 |
| Author(s): | Withee JL; Sen R; Cyert MS; |
| Address: | "Department of Biological Sciences, Stanford University, Stanford, California 94305-5020, USA" |
| DOI: | 10.1093/genetics/149.2.865 |
| ISSN/ISBN: | 0016-6731 (Print) 0016-6731 (Linking) |
| Abstract: | "Calcineurin is a conserved, Ca2+/CaM-stimulated protein phosphatase required for Ca2+-dependent signaling in many cell types. In yeast, calcineurin is essential for growth in high concentrations of Na+, Li+, Mn2+, and OH-, and for maintaining viability during prolonged treatment with mating pheromone. In contrast, the growth of calcineurin-mutant yeast is better than that of wild-type cells in the presence of high concentrations of Ca2+. We identified mutations that suppress multiple growth defects of calcineurin-deficient yeast (cnb1Delta or cna1Delta cna2Delta). Mutations in URE2 suppress the sensitivity of calcineurin mutants to Na+, Li+, and Mn2+, and increase their survival during treatment with mating pheromone. ure2 mutations require both the transcription factor Gln3p and the Na+ ATPase Pmr2p to confer Na+ and Li+ tolerance. Mutations in PMA1, which encodes the yeast plasma membrane H+-ATPase, also suppress many growth defects of calcineurin mutants. pma1 mutants display growth phenotypes that are opposite to those of calcineurin mutants; they are resistant to Na+, Li+, and Mn2+, and sensitive to Ca2+. We also show that calcineurin mutants are sensitive to aminoglycoside antibiotics such as hygromycin B while pma1 mutants are more resistant than wild type. Furthermore, pma1 and calcineurin mutations have antagonistic effects on intracellular [Na+] and [Ca2+]. Finally, we show that yeast expressing a constitutively active allele of calcineurin display pma1-like phenotypes, and that membranes from these yeast have decreased levels of Pma1p activity. These studies further characterize the roles that URE2 and PMA1 play in regulating intracellular ion homeostasis" |
| Keywords: | "Adenosine Triphosphatases/physiology Calcineurin/*deficiency/*genetics/pharmacology Calcium/antagonists & inhibitors/pharmacology *Cation Transport Proteins DNA-Binding Proteins/physiology Drug Resistance, Microbial Enzyme Activation/genetics Fungal Prote;" |
| Notes: | "MedlineWithee, J L Sen, R Cyert, M S eng 5 T32 GM07276/GM/NIGMS NIH HHS/ GM-48729/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. 1998/06/11 Genetics. 1998 Jun; 149(2):865-78. doi: 10.1093/genetics/149.2.865" |
