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Eukaryotic Cell doi:10.1128/EC.00382-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mg²⁺ deprivation elicits rapid Ca²⁺ uptake and activates Ca²⁺/calcineurin signaling in Saccharomyces cerevisiae

Max F. Perutz Laboratories, Department of Genetics, University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria; Institute of Medical Biochemistry & Medical Molecular Biology, Medical University of Graz, Harrachgasse 21/III, A-8010 Graz, Austria; Institute for Prevention and Nutrition, Osterfeldstrae 92, D-85737, Ismaning, Germany

^* To whom correspondence should be addressed. Email: jochen.stadler{at}univie.ac.at.

	Abstract

To 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 is also induced by high Ca²⁺ and/or alkalinization. Among the genes significantly up-regulated by Mg²⁺ starvation, Ca²⁺ 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 signaling pathway. Similarly to Ca²⁺ stress, Mg²⁺ starvation induces translocation of the transcription factor Crz1p from the cytoplasm into the nucleus. The up-regulation of ENA1 and PHO89 upon 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⁺. 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.

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