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

E Smith. et al. The EMBO Journal (2011) 30, 2233–2245

Speaker: Yung-Han Yang (楊詠涵)                                 Time: 13:00~14:00, Oct. 26, 2011

Commentator: Dr. Liang-Yi Hung (洪良宜 老師)        Place: Room 601

Abstract

Centrosomes are microtubule-organizing centers of animal cells. It influences cell shape and polarity and directs the formation of the bipolar mitotic spindle. Duplicated centrosomes separate in late G2 phase and form the poles of the mitotic spindle. Cyclin dependent kinase 1 (Cdk1) is thought to trigger this process by phosphorylating the motor protein Eg5 at Thr927. However, the precise control mechanism of centrosome separation remains to be understood. Here they report that in G2 phase Eg5 and Polo like kinase 1 (Plk1) can drive centrosome separation independently of Cdk1. Accordingly, Cdk2 can compensate for Cdk1, and phosphorylates Eg5 at Thr927. Moreover, Plk1 appears to be required for Cdk1 independent centrosome separation. Using 3D live cell imaging, they find that both Cdk1 and Plk1 can initiate centrosome separation independently of each other, albeit with dramatically different dynamics. Plk1 driven centrosome separation is initiated with a longer time lag. After disjunction, Plk1 driven separation proceeds with slow and staggering movement. Cdk1 initiates separation within minutes of kinase activation and allows fast movement of the centrosomes. It has been suggested that the forces acting on cytoplasmic MTs may include pushing by MT growth at the plus ends, and pulling by MT motors anchored at the cortex or in the the cytoplasm. Strikingly, actin depolymerization, as well as destabilization of interphase 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. Their findings implicate the modulation of MT stability in G2 and M phase as a regulatory element in the control ofcentrosome separation.

References

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2.      Olivier Gavet and Jonathon Pines. 2010. Progressive Activation of cyclinB1-Cdk1Coordinates Entry to Mitosis. Developmental Cell. 18, 533–543.