title: Adaptation to high-salt stress in Saccharomyces cerevisiae is regulated by Ca2+/calmodulin-dependent phosphoprotein phosphatase (calcineurin) and cAMP-dependent protein kinase.
abstract: Ca2+/calmodulin-dependent phosphoprotein phosphatase (calcineurin, PP2B) of Saccharomyces cerevisiae is implicated in adaptation to high-salt conditions. Calcineurin mediates high salt-induced expression of the ENA1/PMR2 gene encoding the P-type ATPase, which is suggested to be involved in Na+ efflux. We identified the PDE1 gene encoding the low-affinity cAMP phosphodiesterase as a multicopy suppressor of the Li(+)- and Na(+)-sensitive calcineurin null mutant, suggesting that cAMP is a negative regulator of adaptation to high-salt stress. Genetic analysis indicated that calcineurin and cAMP act antagonistically in a common pathway for adaptation. The bcy1 disruption, which leads to constitutive cAMP-dependent protein kinase (PKA) activity inhibited high NaCl-induced expression of the ENA1/PMR2 gene, caused an elevation of the intracellular Na+ level and a growth defect in high-NaCl medium, all of which were analogous to the defects of a calcineurin mutant. A reduced cAMP level resulting from multiple copies of the PDE1 gene caused increased expression of the ENA1/PMR2 gene in response to high NaCl. We propose a model for the regulation of cation homeostasis, in which calcineurin antagonizes PKA to activate transcription of the ENA1/PMR2 gene in response to high-salt conditions.
authors.affiliation: Department of Fermentation Technology, Faculty of Engineering, Hiroshima University, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Hirata
authors.forename: S
authors.initials: S
authors.lastname: Harada
authors.forename: H
authors.initials: H
authors.lastname: Namba
authors.forename: T
authors.initials: T
authors.lastname: Miyakawa
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000302:isolation & purification; D000222:Adaptation, Physiological / Q000502:physiology*; D000251:Adenosine Triphosphatases / Q000302:isolation & purification; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins; D002412:Cations; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D015966:Gene Expression Regulation, Fungal; D016153:Genes, Suppressor; D006706:Homeostasis; D008094:Lithium / Q000494:pharmacology*; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D012964:Sodium / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase
chemical_list: D002148:Calmodulin-Binding Proteins; D027682:Cation Transport Proteins; D002412:Cations; C086375:ENA1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D008094:Lithium; D012964:Sodium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase