Sardon Teresa, Peset Isabel, Petrova Boryana, Vernos Isabelle
Cell and Developmental Biology Program, Centre for Genomic Regulation (CRG), UPF, Barcelona, Spain.
EMBO J. 2008 Oct 8;27(19):2567-79. doi: 10.1038/emboj.2008.173. Epub 2008 Aug 28.
The centrosomal kinase Aurora A (AurA) is required for cell cycle progression, centrosome maturation and spindle assembly. However, the way it participates in spindle assembly is still quite unclear. Using the Xenopus egg extract system, we have dissected the role of AurA in the different microtubule (MT) assembly pathways involved in spindle formation. We developed a new tool based on the activation of AurA by TPX2 to clearly define the requirements for localization and activation of the kinase during spindle assembly. We show that localized AurA kinase activity is required to target factors involved in MT nucleation and stabilization to the centrosome, therefore promoting the formation of a MT aster. In addition, AurA strongly enhances MT nucleation mediated by the Ran pathway through cytoplasmic phosphorylation. Altogether, our data show that AurA exerts an effect as a key regulator of MT assembly during M phase and therefore of bipolar spindle formation.
中心体激酶极光激酶A(AurA)是细胞周期进程、中心体成熟和纺锤体组装所必需的。然而,其参与纺锤体组装的方式仍相当不清楚。利用非洲爪蟾卵提取物系统,我们剖析了AurA在纺锤体形成所涉及的不同微管(MT)组装途径中的作用。我们基于TPX2对AurA的激活开发了一种新工具,以明确激酶在纺锤体组装过程中的定位和激活要求。我们表明,局部的AurA激酶活性是将参与MT成核和稳定的因子靶向到中心体所必需的,从而促进MT星状体的形成。此外,AurA通过细胞质磷酸化强烈增强由Ran途径介导的MT成核。总之,我们的数据表明,AurA作为M期MT组装的关键调节因子发挥作用,因此也是双极纺锤体形成的关键调节因子。