Laboratory of Chromosome and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Dev Cell. 2010 Jun 15;18(6):903-12. doi: 10.1016/j.devcel.2010.05.018.
Chromosome-dependent spindle assembly requires the chromosomal recruitment and activation of Aurora B, the kinase subunit of the chromosomal passenger complex (CPC). It remains unclear how the chromosome-activated kinase spatially transmits signals to organize the micron-scale spindle. Here we reveal that the CPC must detect two structures, chromosomes and microtubules, to support spindle assembly in Xenopus egg extracts. While Aurora B is enriched on chromosomes in metaphase, we establish that a fraction of Aurora B is targeted to the metaphase spindle and phosphorylates microtubule-bound substrates. We demonstrate that chromosomally activated Aurora B must be targeted to microtubules to drive spindle assembly. Moreover, although the CPC-microtubule interaction can activate Aurora B, which further promotes microtubule assembly, this positive feedback is not initiated without chromosomes. We propose that the dual detection of chromosomes and microtubules by the CPC is a critical step in assembling spindles around and only around chromosomes.
染色体依赖性纺锤体组装需要 Aurora B 的募集和激活,Aurora B 是染色体乘客复合物(CPC)的激酶亚基。目前尚不清楚激活激酶如何在空间上传递信号以组织微米级别的纺锤体。在这里,我们揭示了 CPC 必须检测两种结构,染色体和微管,以支持非洲爪蟾卵提取物中的纺锤体组装。虽然 Aurora B 在中期染色体上富集,但我们确定一部分 Aurora B 被靶向到中期纺锤体并磷酸化微管结合底物。我们证明,激活的 Aurora B 必须靶向微管以驱动纺锤体组装。此外,尽管 CPC-微管相互作用可以激活 Aurora B,从而进一步促进微管组装,但如果没有染色体,这种正反馈就不会启动。我们提出,CPC 对染色体和微管的双重检测是围绕染色体组装纺锤体的关键步骤,而且只在染色体周围组装纺锤体。