Magidson Valentin, He Jie, Ault Jeffrey G, O'Connell Christopher B, Yang Nachen, Tikhonenko Irina, McEwen Bruce F, Sui Haixin, Khodjakov Alexey
Wadsworth Center, New York State Department of Health, Albany, NY 12201.
Wadsworth Center, New York State Department of Health, Albany, NY 12201 School of Public Health, State University of New York, Albany, NY 12201.
J Cell Biol. 2016 Feb 1;212(3):307-19. doi: 10.1083/jcb.201412139.
Kinetochores attach chromosomes to the spindle microtubules and signal the spindle assembly checkpoint to delay mitotic exit until all chromosomes are attached. Light microscopy approaches aimed to indirectly determine distances between various proteins within the kinetochore (termed Delta) suggest that kinetochores become stretched by spindle forces and compact elastically when the force is suppressed. Low Delta is believed to arrest mitotic progression in taxol-treated cells. However, the structural basis of Delta remains unknown. By integrating same-kinetochore light microscopy and electron microscopy, we demonstrate that the value of Delta is affected by the variability in the shape and size of outer kinetochore domains. The outer kinetochore compacts when spindle forces are maximal during metaphase. When the forces are weakened by taxol treatment, the outer kinetochore expands radially and some kinetochores completely lose microtubule attachment, a condition known to arrest mitotic progression. These observations offer an alternative interpretation of intrakinetochore tension and question whether Delta plays a direct role in the control of mitotic progression.
动粒将染色体附着于纺锤体微管，并向纺锤体组装检查点发出信号，以延迟有丝分裂退出，直到所有染色体都附着。旨在间接确定动粒内各种蛋白质之间距离（称为Delta）的光学显微镜方法表明，动粒会因纺锤体力量而伸展，并在力量被抑制时弹性收缩。低Delta值被认为会阻止紫杉醇处理细胞中的有丝分裂进程。然而，Delta的结构基础仍然未知。通过整合同动粒光学显微镜和电子显微镜，我们证明Delta值受外动粒结构域形状和大小变化的影响。在中期，当纺锤体力量最大时，外动粒会收缩。当通过紫杉醇处理使力量减弱时，外动粒会径向扩张，一些动粒会完全失去微管附着，这种情况已知会阻止有丝分裂进程。这些观察结果为动粒内张力提供了另一种解释，并质疑Delta是否在有丝分裂进程控制中发挥直接作用。
