Sampath Srinath C, Ohi Ryoma, Leismann Oliver, Salic Adrian, Pozniakovski Andrei, Funabiki Hironori
Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10021, USA.
Cell. 2004 Jul 23;118(2):187-202. doi: 10.1016/j.cell.2004.06.026.
In cells lacking centrosomes, such as those found in female meiosis, chromosomes must nucleate and stabilize microtubules in order to form a bipolar spindle. Here we report the identification of Dasra A and Dasra B, two new components of the vertebrate chromosomal passenger complex containing Incenp, Survivin, and the kinase Aurora B, and demonstrate that this complex is required for chromatin-induced microtubule stabilization and spindle formation. The failure of microtubule stabilization caused by depletion of the chromosomal passenger complex was rescued by codepletion of the microtubule-depolymerizing kinesin MCAK, whose activity is negatively regulated by Aurora B. By contrast, we present evidence that the Ran-GTP pathway of chromatin-induced microtubule nucleation does not require the chromosomal passenger complex, indicating that the mechanisms of microtubule assembly by these two pathways are distinct. We propose that the chromosomal passenger complex regulates local MCAK activity to permit spindle formation via stabilization of chromatin-associated microtubules.
在缺乏中心体的细胞中，比如在雌性减数分裂中发现的那些细胞，染色体必须使微管成核并使其稳定，以便形成双极纺锤体。在此我们报告鉴定出Dasra A和Dasra B，它们是脊椎动物染色体乘客复合体的两个新组分，该复合体包含Incenp、Survivin和激酶Aurora B，并证明该复合体对于染色质诱导的微管稳定和纺锤体形成是必需的。通过共缺失微管解聚驱动蛋白MCAK可挽救因染色体乘客复合体缺失而导致的微管稳定失败，MCAK的活性受到Aurora B的负调控。相比之下，我们提供的证据表明，染色质诱导的微管成核的Ran - GTP途径不需要染色体乘客复合体，这表明这两条途径的微管组装机制是不同的。我们提出，染色体乘客复合体调节局部MCAK活性，以通过稳定与染色质相关的微管来允许纺锤体形成。
