Differential control of Eg5-dependent centrosome separation by Plk1 and Cdk1

• Published in: The EMBO journal Vol. 30; no. 11; pp. 2233 - 2245
• Main Authors: Smith, Ewan, Hégarat, Nadia, Vesely, Clare, Roseboom, Isaac, Larch, Chris, Streicher, Hansjörg, Straatman, Kornelis, Flynn, Helen, Skehel, Mark, Hirota, Toru, Kuriyama, Ryoko, Hochegger, Helfrid
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.06.2011; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: actin; Animals; CDC2 Protein Kinase - metabolism; Cell cycle; Cell Cycle Proteins - metabolism; Cell Division; Cell Line; Centrosome - metabolism; Eg5; Humans; Kinases; Kinesins - metabolism; microtubules; mitosis; Molecular biology; Phosphorylation; Polo kinase; Polo-Like Kinase 1; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2011.120

Cyclin‐dependent kinase 1 (Cdk1) is thought to trigger centrosome separation in late G2 phase by phosphorylating the motor protein Eg5 at Thr927. However, the precise control mechanism of centrosome separation remains to be understood. Here, we report that in G2 phase polo‐like kinase 1 (Plk1) can trigger centrosome separation independently of Cdk1. We find that Plk1 is required for both C‐Nap1 displacement and for Eg5 localization on the centrosome. Moreover, Cdk2 compensates for Cdk1, and phosphorylates Eg5 at Thr927. Nevertheless, Plk1‐driven centrosome separation is slow and staggering, while Cdk1 triggers fast movement of the centrosomes. We find that actin‐dependent Eg5‐opposing forces slow down separation in G2 phase. Strikingly, actin depolymerization, as well as destabilization of interphase microtubules (MTs), is sufficient to remove this obstruction and to speed up Plk1‐dependent separation. Conversely, MT stabilization in mitosis slows down Cdk1‐dependent centrosome movement. Our findings implicate the modulation of MT stability in G2 and M phase as a regulatory element in the control of centrosome separation. Mammalian centrosomes separate prior to mitosis in a process involving Cdk1 and the kinesin Eg5. Dissection by chemical genetics reveals a Cdk1‐independent alternative mechanism, in which Plk1 counteracts both centrosomal cohesion factors and Eg5‐opposing cytoskeletal forces.