Laboratory for Developmental Genomics, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Nat Cell Biol. 2011 Jun;13(6):708-14. doi: 10.1038/ncb2242. Epub 2011 May 15.
The assembly of a functional mitotic spindle is crucial for achieving successful mitosis. Aurora A kinase is one of the key regulators of mitotic events, including mitotic entry, centrosome maturation and spindle bipolarity. Caenorhabditis elegans Aurora A (AIR-1) is responsible for the assembly of γ-tubulin-independent microtubules in early embryos; however, the mechanism by which AIR-1 contributes to microtubule assembly during mitosis has been unclear. Here we show by live-cell imaging and RNA-mediated interference (RNAi)-based modulation of gene activity that AIR-1 has a crucial role in the assembly of chromatin-stimulated microtubules that is independent of the γ-tubulin complex. Surprisingly, the kinase activity of AIR-1 is dispensable for this process. Although the kinase-inactive form of AIR-1 was detected along the microtubules as well as on centrosomes, the kinase-active form of AIR-1 was restricted to centrosomes. Thus, we propose that AIR-1 has a kinase-dependent role at centrosomes and a kinase-independent role for stabilizing spindle microtubules and that coordination of these two roles is crucial for the assembly of mitotic spindles.
有丝分裂纺锤体的组装对于实现成功的有丝分裂至关重要。极光激酶 A 是有丝分裂事件的关键调节因子之一,包括有丝分裂进入、中心体成熟和纺锤体两极。秀丽隐杆线虫 Aurora A(AIR-1)负责早期胚胎中γ-微管蛋白独立的微管组装;然而,AIR-1 如何在有丝分裂过程中促进微管组装的机制尚不清楚。在这里,我们通过活细胞成像和基于 RNA 介导的干扰(RNAi)的基因活性调节表明,AIR-1 在组装染色质刺激的微管中具有关键作用,而这种作用与γ-微管蛋白复合物无关。令人惊讶的是,AIR-1 的激酶活性对于这个过程是可有可无的。尽管激酶失活形式的 AIR-1 沿着微管以及中心体被检测到,但激酶活性形式的 AIR-1 仅限于中心体。因此,我们提出 AIR-1 在中心体上具有激酶依赖性作用,以及稳定纺锤体微管的激酶非依赖性作用,并且这两个作用的协调对于有丝分裂纺锤体的组装至关重要。