Regulation of the Na+/K+-ATPase Ena1 Expression by Calcineurin/Crz1 under High pH Stress: A Quantitative Study

PLoS One. 2016 Jun 30;11(6):e0158424. doi: 10.1371/journal.pone.0158424. eCollection 2016.

Abstract

Regulated expression of the Ena1 Na+-ATPase is a crucial event for adaptation to high salt and/or alkaline pH stress in the budding yeast Saccharomyces cerevisiae. ENA1 expression is under the control of diverse signaling pathways, including that mediated by the calcium-regulatable protein phosphatase calcineurin and its downstream transcription factor Crz1. We present here a quantitative study of the expression of Ena1 in response to alkalinization of the environment and we analyze the contribution of Crz1 to this response. Experimental data and mathematical models substantiate the existence of two stress-responsive Crz1-binding sites in the ENA1 promoter and estimate that the contribution of Crz1 to the early response of the ENA1 promoter is about 60%. The models suggest the existence of a second input with similar kinetics, which would be likely mediated by high pH-induced activation of the Snf1 kinase.

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Binding Sites / genetics
  • Calcineurin / metabolism
  • Calcineurin / physiology*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Fungal
  • Hydrogen-Ion Concentration
  • Organisms, Genetically Modified
  • Promoter Regions, Genetic
  • Protein Transport
  • Regulatory Elements, Transcriptional
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / growth & development
  • Saccharomyces cerevisiae* / metabolism
  • Sodium-Potassium-Exchanging ATPase / genetics*
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Stress, Physiological / genetics*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*

Substances

  • CRZ1 protein, S cerevisiae
  • DNA-Binding Proteins
  • ENA1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Calcineurin
  • Sodium-Potassium-Exchanging ATPase

Grants and funding

This work was supported by grants BFU2011-30197-C3-01, BFU2014-54591-C2-1-P and EUI2009-04147 (SysMo2) to JA. (Ministry of Industry and Competitivity, Spain, and Fondo Europeo de Desarrollo Regional [FEDER]). JA is the recipient of an Ajut 2014SGR-4 award (Generalitat de Catalunya). DC was recipient of a predoctoral fellowship from the Spanish Ministry of Education. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.