Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, 69117 Heidelberg, Germany.
Nat Cell Biol. 2010 Dec;12(12):1166-76. doi: 10.1038/ncb2120. Epub 2010 Nov 14.
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.
在间期中，中心体由连接母和子中心粒近端的蛋白连接体保持在一起。该连接体在有丝分裂开始时通过称为中心体分离的过程被拆开，从而促进中心体分离和双极纺锤体的形成。NIMA（无丝分裂 A 相关激酶）相关激酶 Nek2A 通过分离连接蛋白 C-Nap1 和根蛋白来断开中心体的连接。然而，控制中心体分离的机制仍知之甚少。在这里，我们报告了 Hippo 途径的两个组成部分，哺乳动物不育 20 样激酶 2（Mst2）和支架蛋白 Salvador（hSav1），直接与 Nek2A 相互作用，并调节其定位到中心体的能力，以及磷酸化 C-Nap1 和根蛋白。此外，我们证明 hSav1-Mst2-Nek2A 中心体分离途径在部分抑制驱动蛋白-5 Eg5 时对于双极纺锤体的形成变得至关重要。我们提出 hSav1-Mst2-Nek2A 和 Eg5 在中心体分离中具有不同但互补的功能。
