title: Zinc finger protein Prz1 regulates Ca2+ but not Cl- homeostasis in fission yeast. Identification of distinct branches of calcineurin signaling pathway in fission yeast.
abstract: Calcineurin is an important mediator that connects the Ca(2+)-dependent signaling to various cellular responses in a wide variety of cell types and organisms. In budding yeast, activated calcineurin exerts its function mainly by regulating the Crz1p/Tcn1 transcription factor. Here, we cloned the fission yeast prz1(+) gene, which encodes a zinc finger transcription factor highly homologous to Crz1/Tcn1. Similar to the results in budding yeast, calcineurin dephosphorylated Prz1 and resulted in the trans-location of Prz1 from the cytoplasm to the nucleus. Prz1 expression was stimulated by high extracellular Ca(2+) in a calcineurin-dependent fashion. However, unlike in budding yeast, the prz1-null cells did not show any phenotype similar to those previously reported in calcineurin deletion such as aberrant cell morphology, mating defect, or hypersensitivity to Cl(-). Instead, the prz1-null cells showed hypersensitivity to Ca(2+), consistent with a dramatic decrease in transcription of Pmc1 Ca(2+) pump. Interestingly, overexpression of Prz1 did not suppress the Cl(-) hypersensitivity of calcineurin deletion, and overexpression of Pmp1 MAPK phosphatase suppressed the Cl(-) hypersensitivity of calcineurin deletion but not the Ca(2+) hypersensitivity of prz1 deletion. In addition, mutations in the its2(+)/cps1(+), its8(+), and its10(+)/cdc7(+) genes that showed synthetic lethal genetic interaction with calcineurin deletion did not exhibit synthetic lethality with the prz1 deletion. Our results suggest that calcineurin activates at least two distinct signaling branches, i.e. the Prz1-dependent transcriptional regulation and an unknown mechanism, which functions antagonistically with the Pmk1 MAPK pathway.
authors.affiliation: Division of Molecular Pharmacology and Pharmacogenomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Sonoko
authors.initials: S
authors.lastname: Hirayama
authors.forename: Reiko
authors.initials: R
authors.lastname: Sugiura
authors.forename: Yabin
authors.initials: Y
authors.lastname: Lu
authors.forename: Takuya
authors.initials: T
authors.lastname: Maeda
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawagishi
authors.forename: Mistuhiro
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Tohda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Giga-Hama
authors.forename: Hisato
authors.initials: H
authors.lastname: Shuntoh
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kuno
mesh_terms: D000595:Amino Acid Sequence; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D049452:Green Fluorescent Proteins; D015151:Immunoblotting; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000378:metabolism* / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013696:Temperature; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
chemical_list: C109868:CRZ1 protein, S cerevisiae; D002352:Carrier Proteins; D002712:Chlorides; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D008164:Luminescent Proteins; C000593219:Prz1 protein, S pombe; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D019703:Calcineurin; D002118:Calcium