Mg2+Deprivation Elicits Rapid Ca2+Uptake and Activates Ca2+/Calcineurin Signaling inSaccharomyces cerevisiae

ABSTRACTTo learn about the cellular processes involved in Mg2+homeostasis and the mechanisms allowing cells to cope with low Mg2+availability, we performed RNA expression-profiling experiments and followed changes in gene activity upon Mg2+depletion on a genome-wide scale. A striking portion of genes up-regulated under Mg2+depletion are also induced by high Ca2+and/or alkalinization. Among the genes significantly up-regulated by Mg2+starvation, Ca2+stress, and alkalinization areENA1(encoding a P-type ATPase sodium pump) andPHO89(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 Ca2+stress, Mg2+starvation induces translocation of the transcription factor Crz1p from the cytoplasm into the nucleus. The up-regulation ofENA1andPHO89upon Mg2+starvation depends on extracellular Ca2+. Using fluorescence resonance energy transfer microscopy, we demonstrate that removal of Mg2+results in an immediate increase in free cytoplasmic Ca2+. This effect is dependent on external Ca2+. The results presented indicate that Mg2+depletion in yeast cells leads to enhanced cellular Ca2+concentrations, which activate the Crz1p/calcineurin pathway. We provide evidence that calcineurin/Crz1p signaling is crucial for yeast cells to cope with Mg2+depletion stress.