4.8 Article

Calcineurin ensures a link between the DNA replication checkpoint and microtubule-dependent polarized growth

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NATURE CELL BIOLOGY
卷 13, 期 3, 页码 234-U357

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NATURE PUBLISHING GROUP
DOI: 10.1038/ncb2166

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  1. Ministry of Education, Science, and Culture of Japan
  2. Cancer Research UK

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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 Teal. Importantly, NETO delay requires activation of calcineurin, which is carried out by Cdsl, resulting in Tip1 dephosphorylation. Thus, our study establishes a critical link between calcineurin and checkpoint-dependent cell morphogenesis.

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