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Eukaryotic Cell, April 2007, p. 592-599, Vol. 6, No. 4
1535-9778/07/$08.00+0     doi:10.1128/EC.00382-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Mg2+ Deprivation Elicits Rapid Ca2+ Uptake and Activates Ca2+/Calcineurin Signaling in Saccharomyces cerevisiae{triangledown}

Gerlinde Wiesenberger,1 Katarina Steinleitner,1 Roland Malli,2 Wolfgang F. Graier,2 Jürgen Vormann,3 Rudolf J. Schweyen,1 and Jochen A. Stadler1*

Max F. Perutz Laboratories, Department of Genetics, University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria,1 Institute of Medical Biochemistry & Medical Molecular Biology, Medical University of Graz, Harrachgasse 21/III, A-8010 Graz, Austria,2 Institute for Prevention and Nutrition, Adalperostraße 37, D-85737, Ismaning, Germany3

Received 5 December 2006/ Accepted 15 February 2007

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 are 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 (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 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+. 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.

* Corresponding author. Mailing address: Max F. Perutz Laboratories, Department of Genetics, University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria. Phone: 43-1-4277-54614. Fax: 43-1-4277-9548. E-mail: jochen.stadler{at}univie.ac.at

{triangledown} Published ahead of print on 2 March 2007.

Eukaryotic Cell, April 2007, p. 592-599, Vol. 6, No. 4
1535-9778/07/$08.00+0     doi:10.1128/EC.00382-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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