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Cdk1 依赖性磷酸化 KIF4A 的 S1186 位点在早期有丝分裂过程中触发染色体的侧向压缩。

Cdk1-dependent phosphorylation of KIF4A at S1186 triggers lateral chromosome compaction during early mitosis.

机构信息

Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, Japan.

Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Osaka, Japan.

出版信息

PLoS One. 2018 Dec 21;13(12):e0209614. doi: 10.1371/journal.pone.0209614. eCollection 2018.

Abstract

Chromosome organization during cell division is achieved through the timely association of proteins with chromatin and is regulated by protein phosphorylation. Kinesin family member 4A (KIF4A) plays an important role in the chromosome organization through the formation of the chromosome scaffold structure. However, the relationship between the function of KIF4A and its phosphorylation remains unclear. Here, we demonstrate that Cdk1-dependent phosphorylation of KIF4A at S1186 is required for chromosome binding and chromosome scaffold formation. The KIF4A mutant, which is not phosphorylated at S1186, was found to localize to the nucleus during interphase but did not accumulate in the chromosome scaffold after nuclear envelope breakdown. In addition, defects in KIF4A phosphorylation were found to disrupt the interaction of KIF4A with the condensin I complex. As a result, the morphology of the chromosomes was observed to be laterally decondensed, without condensin I in the chromosome scaffold. Additionally, a defect in chromosome segregation, chromosome bridge formation, was often observed. Although both KIF4A and condensin I disappeared from the chromosomes, the chromosomal localization of condensin II was not affected. Collectively, our novel results revealed that Cdk1-dependent KIF4A phosphorylation at S1186 is a trigger for chromosomal organization during early mitosis.

摘要

在细胞分裂过程中,染色体的组织是通过蛋白质与染色质的适时结合来实现的,并且受到蛋白质磷酸化的调控。驱动蛋白家族成员 4A(KIF4A)通过形成染色体支架结构,在染色体的组织中发挥着重要作用。然而,KIF4A 的功能与其磷酸化之间的关系尚不清楚。在这里,我们证明了 Cdk1 依赖性磷酸化 KIF4A 的 S1186 位点对于染色体结合和染色体支架的形成是必需的。我们发现,不能磷酸化 S1186 的 KIF4A 突变体在核膜崩解后不能积累在染色体支架中,但在有丝分裂间期仍定位于核内。此外,KIF4A 磷酸化的缺陷被发现会破坏 KIF4A 与凝聚素 I 复合物的相互作用。结果,观察到染色体的形态呈侧向去凝聚,在染色体支架中没有凝聚素 I。此外,还经常观察到染色体分离、染色体桥形成的缺陷。尽管 KIF4A 和凝聚素 I 都从染色体上消失了,但凝聚素 II 在染色体上的定位并没有受到影响。总的来说,我们的新结果揭示了 Cdk1 依赖性 KIF4A 磷酸化 S1186 是早期有丝分裂过程中染色体组织的触发因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be87/6303012/24c30b07cd1a/pone.0209614.g001.jpg

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