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1 Division of Molecular Pharmacology and Pharmacogenomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
2 Department of Life Sciences, Faculty of Agriculture, Kagawa University, 761-0795, Japan
3 Faculty of Health Science, Kobe University School of Medicine, Kobe 650-0142, Japan
Schizosaccharomyces pombe pmr1+ gene is homologous to Saccharomyces cerevisiae PMR1 gene, which encodes the P-type Ca2+/Mn2+-ATPase. Addition of Mn2+, as well as Ca2+, to the medium induced pmr1+ gene expression in a calcineurin-dependent manner. The pmr1 knockout (
pmr1) cells exhibited hypersensitivity to EGTA. A screen for high gene dosage-suppressors of the EGTA-hypersensitive phenotype of pmr1 led to the identification of pdt1+ gene, which encodes an Nramp-related metal transporter. The pmr1 cells showed round cell morphology. Although pdt1 cells appeared normal in the regular medium, it showed round cell morphology similar to that of the pmr1 cells when Mn2+ was removed from the medium. The removal of Mn2+ also exacerbated the round morphology of the pmr1 cells. The pmr1pdt1 double mutants grew very slowly and showed extremely aberrant cell morphology with round, enlarged and depolarized shape. The addition of Mn2+, but not Ca2+, to the medium completely suppressed the morphological defects, while both Mn2+ and Ca2+ markedly improved the slow growth of the double mutants. These results suggest that Pmr1 and Pdt1 cooperatively regulate cell morphogenesis through the control of Mn2+ homeostasis, and that calcineurin functions as a Mn2+ sensor as well as a Mn2+ homeostasis regulator.
* Correspondence: E-mail: tkuno{at}med.kobe-u.ac.jp
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