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

Abstract：

: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.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Mardin BR,Lange C,Baxter JE,Hardy T,Scholz SR,Fry AM,Schiebel E

doi

10.1038/ncb2120

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

1166-76

issue

12

eissn

1465-7392

issn

1476-4679

pii

ncb2120

journal_volume

12

pub_type

杂志文章

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