Hachet Virginie, Canard Coralie, Gönczy Pierre
Swiss Institute for Experimental Cancer Research (ISREC), and School of Life Sciences, Swiss Federal Institute of Technology (EPFL), CH-1066 Lausanne, Switzerland.
Dev Cell. 2007 Apr;12(4):531-41. doi: 10.1016/j.devcel.2007.02.015.
Several mitotic regulators, including Cyclin B1/Cdk1, are present at centrosomes prior to mitosis onset, but it is unclear whether centrosomes promote mitotic entry in vivo. Here we developed a sensitive assay in C. elegans embryos for the temporal analysis of mitotic entry, in which the male and female pronuclei undergo asynchronous entry into mitosis when separated from one another. Using this assay, we found that centrosome integrity is necessary for timing mitotic entry. Centrosomes do not function in this instance through their ability to nucleate microtubules. Instead, centrosomes serve to focus the Aurora A kinase AIR-1, which is essential for timely mitotic entry. Furthermore, analysis of embryos in which centrosomes and pronuclei are detached from one another demonstrates that centrosomes are sufficient to promote mitosis onset. Together, our findings support a model in which centrosomes serve as integrative centers for mitotic regulators and thus trigger mitotic entry in a timely fashion.
包括细胞周期蛋白B1/细胞周期蛋白依赖性激酶1（Cyclin B1/Cdk1）在内的几种有丝分裂调节因子在有丝分裂开始前就存在于中心体中，但尚不清楚中心体在体内是否促进有丝分裂的进入。在这里，我们在秀丽隐杆线虫胚胎中开发了一种灵敏的检测方法，用于对有丝分裂进入进行时间分析，在该方法中，当雄原核和雌原核彼此分离时，它们会异步进入有丝分裂。使用该检测方法，我们发现中心体完整性对于有丝分裂进入的时间调控是必要的。在此情况下，中心体并非通过其成核微管的能力发挥作用。相反，中心体起到聚焦极光激酶A（Aurora A kinase）AIR-1的作用，而AIR-1对于及时进入有丝分裂至关重要。此外，对中心体与原核彼此分离的胚胎进行分析表明，中心体足以促进有丝分裂的开始。总之，我们的研究结果支持一种模型，即中心体作为有丝分裂调节因子的整合中心，从而及时触发有丝分裂的进入。
