Mg super(2+) Deprivation Elicits Rapid Ca super(2+) Uptake and Activates Ca super(2+)/Calcineurin Signaling in Saccharomyces cerevisiae

To learn about the cellular processes involved in Mg super(2+) homeostasis and the mechanisms allowing cells to cope with low Mg super(2+) availability, we performed RNA expression-profiling experiments and followed changes in gene activity upon Mg super(2+) depletion on a genome-wide scale. A striking portion of genes up-regulated under Mg super(2+) depletion are also induced by high Ca super(2+) and/or alkalinization. Among the genes significantly up-regulated by Mg super(2+) starvation, Ca super(2+) stress, and alkalinization are ENA1 (encoding a P-type ATPase sodium pump) and PHO89 (encoding a sodium/phosphate cotransporter). We show that up-regulation of these genes is dependent on the calcineurin/Crz1p (calcineurin-responsive zinc finger protein) signaling pathway. Similarly to Ca super(2+) stress, Mg super(2+) starvation induces translocation of the transcription factor Crz1p from the cytoplasm into the nucleus. The up-regulation of ENA1 and PHO89 upon Mg super(2+) starvation depends on extracellular Ca super(2+). Using fluorescence resonance energy transfer microscopy, we demonstrate that removal of Mg super(2+) results in an immediate increase in free cytoplasmic Ca super(2+). This effect is dependent on external Ca super(2+). The results presented indicate that Mg super(2+) depletion in yeast cells leads to enhanced cellular Ca super(2+) concentrations, which activate the Crz1p/calcineurin pathway. We provide evidence that calcineurin/Crz1p signaling is crucial for yeast cells to cope with Mg super(2+) depletion stress.