Plk4-induced centriole biogenesis in human cells
Plk4-induced centriole biogenesis in human cells
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DOI：
10.1016/j.devcel.2007.07.002
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发表时间：
2007-08-01
影响因子：
11.8
通讯作者：
Nigg, Erich A.
中科院分区：
文献类型：
--
作者：
Kleylein-Sohn, Julia;Westendorf, Jens;Nigg, Erich A.
我们发现，Polo样激酶4（Plk 4）在人类细胞中的过度表达诱导中心体扩增，通过同时产生多个原中心粒毗邻每个亲本中心粒。这提供了一个机会，解剖中心粒组装和表征组装中间体。通过siRNA鉴定关键组分并将其排序到组装途径中，并通过免疫电子显微镜进行定位。Plk 4、hSas-6、CPAP、Cep 135、γ-微管蛋白和CP 110在原中心粒形成的不同阶段是必需的，并与不同的中心粒结构相关。值得注意的是，hSas-6仅与新生的原中心粒短暂相关，而Cep 135和CPAP在亲本和新生中心粒的近端管腔内形成核心结构。最后，CP 1 10被早期募集，然后与生长的远端尖端相关，这表明中心粒通过在CP 1 10帽下方插入α-/β-微管蛋白而伸长。总的来说，这些数据提供了一个全面的看法，在人类细胞中的中心粒生物发生的组装途径。
We show that overexpression of Polo-like kinase 4 (Plk4) in human cells induces centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole. This provided an opportunity for dissecting centriole assembly and characterizing assembly intermediates. Critical components were identified and ordered into an assembly pathway through siRNA and localized through immunoelectron microscopy. Plk4, hSas-6, CPAP, Cep135, gamma-tubulin, and CP110 were required at different stages of procentriole formation and in association with different centriolar structures. Remarkably, hSas-6 associated only transiently with nascent procentrioles, whereas Cep135 and CPAP formed a core structure within the proximal lumen of both parental and nascent centrioles. Finally, CP1 10 was recruited early and then associated with the growing distal tips, indicating that centrioles elongate through insertion of alpha-/beta-tubulin underneath a CP1 10 cap. Collectively, these data afford a comprehensive view of the assembly pathway underlying centriole biogenesis in human cells.