Stumpff Jason, von Dassow George, Wagenbach Michael, Asbury Charles, Wordeman Linda
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA.
Dev Cell. 2008 Feb;14(2):252-62. doi: 10.1016/j.devcel.2007.11.014.
During vertebrate cell division, chromosomes oscillate with periods of smooth motion interrupted by abrupt reversals in direction. These oscillations must be spatially constrained in order to align and segregate chromosomes with high fidelity, but the molecular mechanism for this activity is uncertain. We report here that the human kinesin-8 Kif18A has a primary role in the control of chromosome oscillations. Kif18A accumulates as a gradient on kinetochore microtubules in a manner dependent on its motor activity. Quantitative analyses of kinetochore movements reveal that Kif18A reduces the amplitude of preanaphase oscillations and slows poleward movement during anaphase. Thus, the microtubule-depolymerizing kinesin Kif18A has the unexpected function of suppressing chromosome movements. Based on these findings, we propose a molecular model in which Kif18A regulates kinetochore microtubule dynamics to control mitotic chromosome positioning.
在脊椎动物细胞分裂过程中,染色体以平滑运动的周期振荡,期间会被突然的方向反转打断。这些振荡必须在空间上受到限制,以便高精度地对齐和分离染色体,但这种活动的分子机制尚不清楚。我们在此报告,人类驱动蛋白-8 Kif18A在控制染色体振荡中起主要作用。Kif18A以依赖其运动活性的方式在动粒微管上呈梯度积累。对动粒运动的定量分析表明,Kif18A降低了前期振荡的幅度,并在后期减缓了向极运动。因此,微管解聚驱动蛋白Kif18A具有抑制染色体运动的意外功能。基于这些发现,我们提出了一个分子模型,其中Kif18A调节动粒微管动力学以控制有丝分裂染色体定位。