Li Chenyu, Zhang Yajun, Yang Qiaoyun, Ye Fan, Sun Stella Ying, Chen Ee Sin, Liou Yih-Cherng
Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, 117543, Republic of Singapore.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.
Sci Rep. 2016 Jan 6;6:18773. doi: 10.1038/srep18773.
Nucleolar and spindle-associated protein (NuSAP) is a microtubule-associated protein that functions as a microtubule stabiliser. Depletion of NuSAP leads to severe mitotic defects, however the mechanism by which NuSAP regulates mitosis remains elusive. In this study, we identify the microtubule depolymeriser, mitotic centromere-associated kinesin (MCAK), as a novel binding partner of NuSAP. We show that NuSAP regulates the dynamics and depolymerisation activity of MCAK. Phosphorylation of MCAK by Aurora B kinase, a component of the chromosomal passenger complex, significantly enhances the interaction of NuSAP with MCAK and modulates the effects of NuSAP on the depolymerisation activity of MCAK. Our results reveal an underlying mechanism by which NuSAP controls kinetochore microtubule dynamics spatially and temporally by modulating the depolymerisation function of MCAK in an Aurora B kinase-dependent manner. Hence, this study provides new insights into the function of NuSAP in spindle formation during mitosis.
核仁与纺锤体相关蛋白（NuSAP）是一种微管相关蛋白，其功能为微管稳定剂。NuSAP的缺失会导致严重的有丝分裂缺陷，然而NuSAP调节有丝分裂的机制仍不清楚。在本研究中，我们鉴定出微管解聚酶——有丝分裂着丝粒相关驱动蛋白（MCAK）——为NuSAP的一种新结合伴侣。我们发现NuSAP调节MCAK的动力学和解聚活性。染色体乘客复合体的组成部分极光激酶B（Aurora B kinase）对MCAK的磷酸化显著增强了NuSAP与MCAK的相互作用，并调节NuSAP对MCAK解聚活性的影响。我们的结果揭示了一种潜在机制，即NuSAP通过以极光激酶B依赖的方式调节MCAK的解聚功能，在空间和时间上控制着丝粒微管动力学。因此，本研究为NuSAP在有丝分裂期间纺锤体形成中的功能提供了新见解。
