Pmr1, a P-type ATPase, and Pdt1, an Nramp homologue, cooperatively regulate cell morphogenesis in fission yeast: The importance of Mn²⁺ homeostasis

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 (Δpmr1) cells exhibited hypersensitivity to EGTA. A screen for high gene dosage-suppressors of the EGTA-hypersensitive phenotype of Δpmr1 led to the identification of pdt1⁺ gene, which encodes an Nramp-related metal transporter. The Δpmr1 cells showed round cell morphology. Although Δpdt1 cells appeared normal in the regular medium, it showed round cell morphology similar to that of the Δpmr1 cells when Mn²⁺ was removed from the medium. The removal of Mn²⁺ also exacerbated the round morphology of the Δpmr1 cells. The Δpmr1 Δpdt1 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⁺ homeo-stasis regulator.