Kinetochore components are required for central spindle assembly.
Kinetochore components are required for central spindle assembly.
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DOI：
10.1038/ncb3150
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发表时间：
2015-05
影响因子：
21.3
通讯作者：
Dumont J
中科院分区：
文献类型：
--
作者：
Maton G;Edwards F;Lacroix B;Stefanutti M;Laband K;Lieury T;Kim T;Espeut J;Canman JC;Dumont J
一个关键的结构，准备协调染色体分离与分裂平面的规范是中央纺锤体之间形成的分离染色体后，后期开始。中央纺锤体作为一个信号中心，集中蛋白质的分裂平面规范和收缩环收缩。然而，控制中心纺锤体组装初始阶段的分子机制仍然难以捉摸。利用秀丽隐杆线虫受精卵，我们发现微管捆绑蛋白SPD-1 PRC 1和马达ZEN-4 MKLP-1是其伸长过程中适当的中心纺锤体结构所必需的。相比之下，我们发现着丝粒控制的启动中央纺锤体组装。具体而言，中央纺锤体微管组装依赖于骨架蛋白KNL-1以及下游伙伴BUB-1、HCP-1/2CENP-F和CLS-2CLASP的动粒募集;并且受动粒相关蛋白磷酸酶1（PP 1）活性负调控。这反过来又促进CLS-2CLASP的中心纺锤体定位和通过其微管聚合酶活性的初始中心纺锤体微管组装。总之，我们的研究结果揭示了一个保守的动粒蛋白网络在耦合细胞分裂的两个关键事件：染色体分离和胞质分裂中的意想不到的作用。
A critical structure poised to coordinate chromosome segregation with division plane specification is the central spindle that forms between separating chromosomes after anaphase onset. The central spindle acts as a signaling center that concentrates proteins essential for division plane specification and contractile ring constriction. However, the molecular mechanisms that control the initial stages of central spindle assembly remain elusive. Using Caenorhabditis elegans zygotes, we found that the microtubule bundling protein SPD-1PRC1 and the motor ZEN-4MKLP-1 are required for proper central spindle structure during its elongation. By contrast, we found that the kinetochore controls the initiation of central spindle assembly. Specifically, central spindle microtubule assembly is dependent upon kinetochore recruitment of the scaffold protein KNL-1, as well as downstream partners BUB-1, HCP-1/2CENP-F, and CLS-2CLASP; and is negatively regulated by kinetochore-associated protein phosphatase 1 (PP1) activity. This in turn promotes central spindle localization of CLS-2CLASP and initial central spindle microtubule assembly through its microtubule polymerase activity. Together, our results reveal an unexpected role for a conserved kinetochore protein network in coupling two critical events of cell division: chromosome segregation and cytokinesis.