Chromosome segregation in mitosis is orchestrated by the interaction of the kinetochore with spindle microtubules. Our recent study shows that NEK2A interacts with MAD1 at the kinetochore and possibly functions as a novel integrator of spindle checkpoint signaling. However, it is unclear how NEK2A regulates kinetochore-microtubule attachment in mitosis. Here we show that NEK2A phosphorylates human Sgo1 and such phosphorylation is essential for faithful chromosome congression in mitosis. NEK2A binds directly to HsSgo1 in vitro and co-distributes with HsSgo1 to the kinetochore of mitotic cells. Our in vitro phosphorylation experiment demonstrated that HsSgo1 is a substrate of NEK2A and the phosphorylation sites were mapped to Ser(14) and Ser(507) as judged by the incorporation of (32)P. Although such phosphorylation is not required for assembly of HsSgo1 to the kinetochore, expression of non-phosphorylatable mutant HsSgo1 perturbed chromosome congression and resulted in a dramatic increase in microtubule attachment errors, including syntelic and monotelic attachments. These findings reveal a key role for the NEK2A-mediated phosphorylation of HsSgo1 in orchestrating dynamic kinetochore-microtubule interaction. We propose that NEK2A-mediated phosphorylation of human Sgo1 provides a link between centromeric cohesion and spindle microtubule attachment at the kinetochores.

中文翻译：

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NEK2A对人Sgo1的磷酸化对于有丝分裂中的染色体转换至关重要。

线粒体与纺锤体微管之间的相互作用精心安排了有丝分裂中的染色体分离。我们最近的研究表明，NEK2A在线粒体上与MAD1相互作用，并可能充当纺锤体检查点信号的新型整合子。但是，目前尚不清楚NEK2A如何调节有丝分裂中的动线粒体-微管附着。在这里，我们显示NEK2A使人Sgo1磷酸化，而这种磷酸化对于有丝分裂中忠实的染色体转换是必不可少的。NEK2A在体外直接与HsSgo1结合，并与HsSgo1共分布到有丝分裂细胞的动粒。我们的体外磷酸化实验表明，HsSgo1是NEK2A的底物，并且通过结合（32）P判断磷酸化位点定位于Ser（14）和Ser（507）。尽管HsSgo1组装到线粒体中不需要这种磷酸化，但不可磷酸化突变体HsSgo1的表达扰乱了染色体国会，并导致微管附着错误（包括同构和单指附着）急剧增加。这些发现揭示了NEK2A介导的HsSgo1磷酸化在动态动粒-微管相互作用中的关键作用。我们建议，NEK2A介导的人类Sgo1的磷酸化提供着丝粒凝聚力和纺锤体的纺锤体微管附着之间的联系。这些发现揭示了NEK2A介导的HsSgo1磷酸化在动态动粒-微管相互作用中的关键作用。我们建议，NEK2A介导的人类Sgo1的磷酸化提供着丝粒凝聚力和纺锤体的纺锤体微管附着之间的联系。这些发现揭示了NEK2A介导的HsSgo1磷酸化在动态动粒-微管相互作用中的关键作用。我们建议，NEK2A介导的人类Sgo1的磷酸化提供着丝粒凝聚力和纺锤体的纺锤体微管附着之间的联系。