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G3 (Bethesda). 2019 Aug 8;9(8):2667-2676. doi: 10.1534/g3.119.400281.

Coordinated Roles of the Putative Ceramide-Conjugation Protein, Cwh43, and a Mn2+-Transporting, P-Type ATPase, Pmr1, in Fission Yeast.

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G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan
G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan.


Genetically controlled mechanisms of cell division and quiescence are vital for responding to changes in the nutritional environment and for cell survival. Previously, we have characterized temperature-sensitive (ts) mutants of the cwh43 gene in fission yeast, Schizosaccharomyces pombe, which is required for both cell proliferation and nitrogen starvation-induced G0 quiescence. Cwh43 encodes an evolutionarily conserved transmembrane protein that localizes in endoplasmic reticulum (ER). Defects in this protein fail to divide in low glucose and lose mitotic competence under nitrogen starvation, and also affect lipid metabolism. Here, we identified mutations of the pmr1 gene, which encodes an evolutionarily conserved Ca2+/Mn2+-transporting P-type ATPase, as potent extragenic suppressors of ts mutants of the cwh43 gene. Intriguingly, these pmr1 mutations specifically suppressed the ts phenotype of cwh43 mutants, among five P-type Ca2+- and/or Mn2+-ATPases reported in this organism. Cwh43 and Pmr1 co-localized in the ER. In cwh43 mutant cells, addition of excessive manganese to culture media enhanced the severe defect in cell morphology, and caused abnormal accumulation of a cell wall component, 1, 3-β-glucan. In contrast, these abnormal phenotypes were abolished by deletion of the pmr1 + gene, as well as by removal of Mn2+ from the culture medium. Furthermore, nutrition-related phenotypes of cwh43 mutant cells were rescued in the absence of Pmr1. Our findings indicate that the cellular processes regulated by Cwh43 are appropriately balanced with Pmr1-mediated Mn2+ transport into the ER.


Cwh43; Pmr1; fission yeast; manganese; nutrient

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