Abstract
Formation of a bipolar spindle is essential for faithful chromosome segregation at mitosis. Because centrosomes define spindle poles, defects in centrosome number and structural organization can lead to a loss of bipolarity1. In addition, microtubule-mediated pulling and pushing forces acting on centrosomes and chromosomes are also important for bipolar spindle formation2. Polo-like kinase 1 (Plk1) is a highly conserved Ser/Thr kinase that has essential roles in the formation of a bipolar spindle with focused poles3,4,5. However, the mechanism by which Plk1 regulates spindle-pole formation is poorly understood. Here, we identify a novel centrosomal substrate of Plk1, Kizuna (Kiz), depletion of which causes fragmentation and dissociation of the pericentriolar material from centrioles at prometaphase, resulting in multipolar spindles. We demonstrate that Kiz is critical for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation, and suggest that Plk1 maintains the integrity of the spindle poles by phosphorylating Kiz.
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Acknowledgements
We thank R. Fukunaga for λGEX–5 HeLa cDNA library and kind advice on solid-phase phosphorylation screening, Y. Ono for antibodies against pericentrin–kendrin, CG-NAP and GCP2, and pTB701–HA–kendrin expression plasmids. S. Tsukita for antibodies against ODF2 and ninein, Y. Watanabe for Plk1 siRNA, N. Nomura for help in RNAi experiments. R. F. Whittier, Y. Watanabe, K. Tanaka, N. Tokai-Nishizumi and K. Yokoyama for helpful discussions. This work was supported by grants-in-aid from the Japan Society for the Promotion of Science and from the Ministry of Education, Cultures, Sports, Science and Technology, Japan.
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Oshimori, N., Ohsugi, M. & Yamamoto, T. The Plk1 target Kizuna stabilizes mitotic centrosomes to ensure spindle bipolarity. Nat Cell Biol 8, 1095–1101 (2006). https://doi.org/10.1038/ncb1474
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DOI: https://doi.org/10.1038/ncb1474
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