title: Casein kinase 1γ ensures monopolar growth polarity under incomplete DNA replication downstream of Cds1 and calcineurin in fission yeast.
abstract: Cell polarity is essential for various cellular functions during both proliferative and developmental stages, and it displays dynamic alterations in response to intracellular and extracellular cues. However, the molecular mechanisms underlying spatiotemporal control of polarity transition are poorly understood. Here, we show that fission yeast Cki3 (a casein kinase 1γ homolog) is a critical regulator to ensure persistent monopolar growth during S phase. Unlike the wild type, cki3 mutant cells undergo bipolar growth when S phase is blocked, a condition known to delay transition from monopolar to bipolar growth (termed NETO [new end takeoff]). Consistent with this role, Cki3 kinase activity is substantially increased, and cells lose their viability in the absence of Cki3 upon an S-phase block. Cki3 acts downstream of the checkpoint kinase Cds1/Chk2 and calcineurin, and the latter physically interacts with Cki3. Autophosphorylation in the C terminus is inhibitory toward Cki3 kinase activity, and calcineurin is responsible for its dephosphorylation. Cki3 localizes to the plasma membrane, and this localization requires the palmitoyltransferase complex Erf2-Erf4. Membrane localization is needed not only for proper NETO timing but also for Cki3 kinase activity. We propose that Cki3 acts as a critical inhibitor of cell polarity transition under S-phase arrest.
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, London, United Kingdom.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Koyano
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Konishi
authors.affiliation: University of Lausanne, Department of Fundamental Microbiology, Lausanne, Switzerland.
authors.forename: Sophie G
authors.initials: SG
authors.lastname: Martin
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ohya
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Hirata
authors.affiliation: Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, London, United Kingdom takashi.toda@cancer.org.uk kume513@hiroshima-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Toda
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan takashi.toda@cancer.org.uk kume513@hiroshima-u.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kume
mesh_terms: D000595:Amino Acid Sequence; D019703:Calcineurin / Q000378:metabolism*; D047389:Casein Kinase I / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D064447:Checkpoint Kinase 2 / Q000378:metabolism*; D004261:DNA Replication; D017353:Gene Deletion; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012568:Schizosaccharomyces / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D064447:Checkpoint Kinase 2; D047389:Casein Kinase I; C578636:Cds1 protein, S pombe; C000599100:Cki3 protein, S pombe; D019703:Calcineurin