The Plk1 target Kizuna stabilizes mitotic centrosomes to ensure spindle bipolarity
The Plk1 target Kizuna stabilizes mitotic centrosomes to ensure spindle bipolarity
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DOI：
10.1038/ncb1474
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发表时间：
2006-10-01
影响因子：
21.3
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
--
作者：
Oshimori, Naoki;Ohsugi, Miho;Yamamoto, Tadashi
双极纺锤体的形成是有丝分裂时染色体分离的关键。由于中心体定义了纺锤体的两极，中心体数量和结构组织的缺陷可能导致双极性的丧失（1）。此外，作用于中心体和染色体的微管介导的拉力和推力对于双极纺锤体的形成也很重要（2）。Polo样激酶1（Plk 1）是一种高度保守的Ser/Thr激酶，在形成具有聚焦极的双极纺锤体中具有重要作用（3-5）。然而，Plk 1调节纺锤极形成的机制知之甚少。在这里，我们发现了Plk 1的一种新型中心体底物Kizuna（Kiz），它的缺失会导致分裂前期中心粒周围物质的断裂和解离，从而产生多极纺锤体。我们证明，Kiz是建立一个强大的有丝分裂中心体架构，可以忍受的力量，在纺锤体形成过程中的中心体上汇聚的关键，并建议Plk 1保持纺锤体极点的完整性，通过磷酸化Kiz。
Formation of a bipolar spindle is essential for faithful chromosome segregation at mitosis. Because centrosomes define spindle poles, defects in centrosome number and structural organization can lead to a loss of bipolarity(1). In addition, microtubule-mediated pulling and pushing forces acting on centrosomes and chromosomes are also important for bipolar spindle formation(2). Polo-like kinase 1 (Plk1) is a highly conserved Ser/Thr kinase that has essential roles in the formation of a bipolar spindle with focused poles(3-5). However, the mechanism by which Plk1 regulates spindle-pole formation is poorly understood. Here, we identify a novel centrosomal substrate of Plk1, Kizuna (Kiz), depletion of which causes fragmentation and dissociation of the pericentriolar material from centrioles at prometaphase, resulting in multipolar spindles. We demonstrate that Kiz is critical for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation, and suggest that Plk1 maintains the integrity of the spindle poles by phosphorylating Kiz.