Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA.
J Cell Biol. 2018 May 7;217(5):1687-1700. doi: 10.1083/jcb.201708114. Epub 2018 Mar 21.
Mitotic spindle disassembly after chromosome separation is as important as spindle assembly, yet the molecular mechanisms for spindle disassembly are unclear. In this study, we investigated how the chromosomal passenger complex (CPC), which contains the Aurora B kinase Ipl1, swiftly concentrates at the spindle midzone in late anaphase, and we researched the role of this dramatic relocalization during spindle disassembly. We showed that the kinesins Kip1 and Kip3 are essential for CPC relocalization. In cells lacking Kip1 and Kip3, spindle disassembly is severely delayed until after contraction of the cytokinetic ring. Purified Kip1 and Kip3 interact directly with the CPC and recruit it to microtubules in vitro, and single-molecule experiments showed that the CPC diffuses dynamically on microtubules but that diffusion stops when the CPC encounters a Kip1 molecule. We propose that Kip1 and Kip3 trap the CPC at the spindle midzone in late anaphase to ensure timely spindle disassembly.
有丝分裂纺锤体在染色体分离后解体与纺锤体组装同样重要，但纺锤体解体的分子机制尚不清楚。在这项研究中，我们调查了含有 Aurora B 激酶 Ipl1 的染色体乘客复合物（CPC）如何在后期有丝分裂中迅速集中到纺锤体中部，并且我们研究了这种剧烈的重定位在纺锤体解体过程中的作用。我们表明，驱动蛋白 Kip1 和 Kip3 对于 CPC 的重定位是必需的。在缺乏 Kip1 和 Kip3 的细胞中，纺锤体解体严重延迟，直到胞质分裂环收缩之后。纯化的 Kip1 和 Kip3 可以直接与 CPC 相互作用，并在体外将其招募到微管上，单分子实验表明 CPC 在微管上动态扩散，但当 CPC 遇到 Kip1 分子时扩散停止。我们提出，Kip1 和 Kip3 在后期有丝分裂中将 CPC 捕获在纺锤体中部，以确保及时进行纺锤体解体。
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