The State Key Laboratory of Biomembrane and Membrane Bioengineering and The Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, China.
Cell Res. 2012 Sep;22(9):1390-401. doi: 10.1038/cr.2012.61. Epub 2012 Apr 17.
Formation of a bipolar spindle is indispensable for faithful chromosome segregation and cell division. Spindle integrity is largely dependent on the centrosome and the microtubule network. Centrosome protein Cep57 can bundle microtubules in mammalian cells. Its related protein (Cep57R) in Xenopus was characterized as a stabilization factor for microtubule-kinetochore attachment. Here we show that Cep57 is a pericentriolar material (PCM) component. Its interaction with NEDD1 is necessary for the centrosome localization of Cep57. Depletion of Cep57 leads to unaligned chromosomes and a multipolar spindle, which is induced by PCM fragmentation. In the absence of Cep57, centrosome microtubule array assembly activity is weakened, and the spindle length and microtubule density decrease. As a spindle microtubule-binding protein, Cep57 is also responsible for the proper organization of the spindle microtubule and localization of spindle pole focusing proteins. Collectively, these results suggest that Cep57, as a NEDD1-binding centrosome component, could function as a spindle pole- and microtubule-stabilizing factor for establishing robust spindle architecture.
双极纺锤体的形成对于忠实的染色体分离和细胞分裂是必不可少的。纺锤体的完整性在很大程度上依赖于中心体和微管网络。中心体蛋白 Cep57 可以在哺乳动物细胞中束状微管。在爪蟾中，其相关蛋白（Cep57R）被描述为微管-动粒附着的稳定因子。在这里，我们表明 Cep57 是中心粒周围物质（PCM）的组成部分。它与 NEDD1 的相互作用对于 Cep57 的中心体定位是必要的。Cep57 的耗竭导致染色体未对准和多极纺锤体，这是由 PCM 片段化引起的。在没有 Cep57 的情况下，中心体微管阵列组装活性减弱，纺锤体长度和微管密度降低。作为一种纺锤体微管结合蛋白，Cep57 还负责纺锤体微管的适当组织和纺锤体极聚焦蛋白的定位。总之，这些结果表明，Cep57 作为一种与 NEDD1 结合的中心体成分，可以作为稳定纺锤体结构的纺锤体极和微管稳定因子发挥作用。
