Cheerambathur Dhanya K, Prevo Bram, Hattersley Neil, Lewellyn Lindsay, Corbett Kevin D, Oegema Karen, Desai Arshad
Ludwig Institute for Cancer Research, CMM-E Room 3052, 9500 Gilman Drive, La Jolla, CA 92093-0653, USA; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Ludwig Institute for Cancer Research, CMM-E Room 3052, 9500 Gilman Drive, La Jolla, CA 92093-0653, USA; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Dev Cell. 2017 May 22;41(4):424-437.e4. doi: 10.1016/j.devcel.2017.04.013.
During cell division, genome inheritance is orchestrated by microtubule attachments formed at kinetochores of mitotic chromosomes. The primary microtubule coupler at the kinetochore, the Ndc80 complex, is regulated by Aurora kinase phosphorylation of its N-terminal tail. Dephosphorylation is proposed to stabilize kinetochore-microtubule attachments by strengthening electrostatic interactions of the tail with the microtubule lattice. Here, we show that removal of the Ndc80 tail, which compromises in vitro microtubule binding, has no effect on kinetochore-microtubule attachments in the Caenorhabditis elegans embryo. Despite this, preventing Aurora phosphorylation of the tail results in prematurely stable attachments that restrain spindle elongation. This premature stabilization requires the conserved microtubule-binding Ska complex, which enriches at attachment sites prior to anaphase onset to dampen chromosome motion. We propose that Ndc80-tail dephosphorylation promotes stabilization of kinetochore-microtubule attachments via the Ska complex and that this mechanism ensures accurate segregation by constraining chromosome motion following biorientation on the spindle.
在细胞分裂过程中，基因组的遗传由有丝分裂染色体动粒处形成的微管附着来协调。动粒处的主要微管连接蛋白Ndc80复合体，受其N端尾巴的极光激酶磷酸化调控。去磷酸化被认为是通过增强尾巴与微管晶格的静电相互作用来稳定动粒-微管附着。在此，我们表明，去除Ndc80尾巴（这会损害体外微管结合）对秀丽隐杆线虫胚胎中的动粒-微管附着没有影响。尽管如此，阻止尾巴的极光磷酸化会导致过早稳定的附着，从而抑制纺锤体伸长。这种过早稳定需要保守的微管结合Ska复合体，该复合体在后期开始前在附着位点富集，以抑制染色体运动。我们提出，Ndc80尾巴去磷酸化通过Ska复合体促进动粒-微管附着的稳定，并且这种机制通过在纺锤体上双定向后限制染色体运动来确保准确分离。
