title: Pmr1, a P-type ATPase, and Pdt1, an Nramp homologue, cooperatively regulate cell morphogenesis in fission yeast: the importance of Mn2+ homeostasis.
abstract: 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 (Deltapmr1) cells exhibited hypersensitivity to EGTA. A screen for high gene dosage-suppressors of the EGTA-hypersensitive phenotype of Deltapmr1 led to the identification of pdt1+ gene, which encodes an Nramp-related metal transporter. The Deltapmr1 cells showed round cell morphology. Although Deltapdt1 cells appeared normal in the regular medium, it showed round cell morphology similar to that of the Deltapmr1 cells when Mn2+ was removed from the medium. The removal of Mn2+ also exacerbated the round morphology of the Deltapmr1 cells. The Deltapmr1Deltapdt1 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.
authors.affiliation: Division of Molecular Pharmacology and Pharmacogenomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Maeda
authors.forename: Reiko
authors.initials: R
authors.lastname: Sugiura
authors.forename: Ayako
authors.initials: A
authors.lastname: Kita
authors.forename: Mariko
authors.initials: M
authors.lastname: Saito
authors.forename: Lu
authors.initials: L
authors.lastname: Deng
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.forename: Lu
authors.initials: L
authors.lastname: Yabin
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takegawa
authors.forename: Hisato
authors.initials: H
authors.lastname: Shuntoh
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kuno
mesh_terms: D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D043402:Cathepsin A / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D008345:Manganese / Q000378:metabolism*; D018832:Molecular Chaperones / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis / Q000502:physiology*; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D019703:Calcineurin; D002118:Calcium; D000252:Calcium-Transporting ATPases; D043402:Cathepsin A; D027682:Cation Transport Proteins; D002614:Chelating Agents; D004533:Egtazic Acid; D008345:Manganese; D018832:Molecular Chaperones; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; C101767:SSC1 protein, S cerevisiae; C468627:cpy1 protein, S pombe