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

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