Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction

Abstract

The Nek2 kinase directs the separation of duplicated centrosomes. Now the Hippo pathway components hSav1 and Mst2 are shown to regulate the function of Nek2 at the centrosome. This pathway cooperates with the kinesin Eg5 to mediate centrosome separation. During interphase, centrosomes are held together by a proteinaceous linker that connects the proximal ends of the mother and daughter centriole. This linker is disassembled at the onset of mitosis in a process known as centrosome disjunction, thereby facilitating centrosome separation and bipolar spindle formation. The NIMA (never in mitosis A)-related kinase Nek2A is implicated in disconnecting the centrosomes through disjoining the linker proteins C-Nap1 and rootletin. However, the mechanisms controlling centrosome disjunction remain poorly understood. Here, we report that two Hippo pathway components, the mammalian sterile 20-like kinase 2 (Mst2) and the scaffold protein Salvador (hSav1), directly interact with Nek2A and regulate its ability to localize to centrosomes, and phosphorylate C-Nap1 and rootletin. Furthermore, we demonstrate that the hSav1–Mst2–Nek2A centrosome disjunction pathway becomes essential for bipolar spindle formation on partial inhibition of the kinesin-5 Eg5. We propose that hSav1–Mst2–Nek2A and Eg5 have distinct, but complementary functions, in centrosome disjunction.

Cite this article

Mardin, B., Lange, C., Baxter, J. et al. Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat Cell Biol 12, 1166–1176 (2010). https://doi.org/10.1038/ncb2120

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