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

Ewan Smith, Nadia Hégarat, Clare Vesely, Isaac Roseboom, Chris Larch, Hansjörg Streicher, Kornelis Straatman, Helen Flynn, Mark Skehel, Toru Hirota, Ryoko Kuriyama, Helfrid Hochegger

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62 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2233-2245
Number of pages13
JournalEMBO Journal
Volume30
Issue number11
DOIs
StatePublished - Jun 1 2011

Keywords

  • Eg5
  • Polo kinase
  • actin
  • microtubules
  • mitosis

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    Smith, E., Hégarat, N., Vesely, C., Roseboom, I., Larch, C., Streicher, H., Straatman, K., Flynn, H., Skehel, M., Hirota, T., Kuriyama, R., & Hochegger, H. (2011). Differential control of Eg5-dependent centrosome separation by Plk1 and Cdk1. EMBO Journal, 30(11), 2233-2245. https://doi.org/10.1038/emboj.2011.120