title: Calcineurin ensures a link between the DNA replication checkpoint and microtubule-dependent polarized growth.
abstract: Microtubules are central to eukaryotic cell morphogenesis. Microtubule plus-end tracking proteins (+TIPs) transport polarity factors to the cell cortex, thereby playing a key role in both microtubule dynamics and cell polarity. However, the signalling pathway linking +TIPs to cell polarity control remains elusive. Here we show that the fission yeast checkpoint kinase Cds1 (Chk2 homologue) delays the transition of growth polarity from monopolar to bipolar (termed NETO; new-end take-off). The +TIPs CLIP170 homologue Tip1 and kinesin Tea2 are responsible for this delay, which is accompanied by a reduction in microtubule dynamics at the cell tip. Remarkably, microtubule stabilization occurs asymmetrically, prominently at the non-growing cell end, which induces abnormal accumulation of the polarity factor Tea1. Importantly, NETO delay requires activation of calcineurin, which is carried out by Cds1, resulting in Tip1 dephosphorylation. Thus, our study establishes a critical link between calcineurin and checkpoint-dependent cell morphogenesis.
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kume
authors.forename: Takayuki
authors.initials: T
authors.lastname: Koyano
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Kanai
authors.forename: Takashi
authors.initials: T
authors.lastname: Toda
authors.forename: Dai
authors.initials: D
authors.lastname: Hirata
mesh_terms: D019703:Calcineurin / Q000378:metabolism*; D049109:Cell Proliferation; D064447:Checkpoint Kinase 2; D004261:DNA Replication; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D006360:Heat-Shock Proteins; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; D029702:Schizosaccharomyces pombe Proteins; C415481:Tea2 protein, S pombe; C114142:tip1 protein, S pombe; D049452:Green Fluorescent Proteins; D064447:Checkpoint Kinase 2; C578636:Cds1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D019703:Calcineurin