Modulation of yeast alkaline cation tolerance by Ypi1 requires calcineurin

Genetics. 2012 Apr;190(4):1355-64. doi: 10.1534/genetics.112.138370. Epub 2012 Feb 23.


Ypi1 was discovered as an essential protein able to act as a regulatory subunit of the Saccharomyces cerevisiae type 1 protein phosphatase Glc7 and play a key role in mitosis. We show here that partial depletion of Ypi1 causes lithium sensitivity and that high levels of this protein confer a lithium-tolerant phenotype to yeast cells. Remarkably, this phenotype was independent of the role of Ypi1 as a Glc7 regulatory subunit. Lithium tolerance in cells overexpressing Ypi1 was caused by a combination of increased efflux of lithium, mediated by augmented expression of the alkaline cation ATPase ENA1, and decreased lithium influx through the Trk1,2 high-affinity potassium transporters. Deletion of CNB1, encoding the regulatory subunit of the calcineurin phosphatase, blocked Ypi1-induced expression of ENA1, normalized Li(+) fluxes, and abolished the Li(+) hypertolerant phenotype of Ypi1-overexpressing cells. These results point to a complex role of Ypi1 on the regulation of cation homeostasis, largely mediated by the calcineurin phosphatase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Calcineurin / genetics
  • Calcineurin / metabolism*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Homeostasis
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lithium Chloride / metabolism
  • Lithium Chloride / pharmacology
  • Phenotype
  • Phosphoric Monoester Hydrolases / metabolism
  • Plasmids / genetics
  • Plasmids / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism


  • Cation Transport Proteins
  • ENA1 protein, S cerevisiae
  • Intracellular Signaling Peptides and Proteins
  • Saccharomyces cerevisiae Proteins
  • TRK2 protein, S cerevisiae
  • Ypi1 protein, S cerevisiae
  • TRK1 protein, S cerevisiae
  • calcineurin phosphatase
  • Calcineurin
  • Phosphoric Monoester Hydrolases
  • Sodium-Potassium-Exchanging ATPase
  • Lithium Chloride