PDF(Pubmed)
Abstract：
At each cell division, nanometer-scale motors and microtubules give rise to the micron-scale spindle. Many mitotic motors step helically around microtubules in vitro, and most are predicted to twist the spindle in a left-handed direction. However, the human spindle exhibits only slight global twist, raising the question of how these molecular torques are balanced. Here, using lattice light sheet microscopy, we find that anaphase spindles in the epithelial cell line MCF10A have a high baseline twist, and we identify factors that both increase and decrease this twist. The midzone motors KIF4A and MKLP1 are redundantly required for left-handed twist at anaphase, and we show that KIF4A generates left-handed torque in vitro. The actin cytoskeleton also contributes to left-handed twist, but dynein and its cortical recruitment factor LGN counteract it. Together, our work demonstrates that force generators regulate twist in opposite directions from both within and outside the spindle, preventing strong spindle twist during chromosome segregation.
摘要：
在每次细胞分裂时，纳米尺度的电机和微管产生了微米尺度的主轴。许多有丝分裂马达在体外围绕微管螺旋步进，大多数人预计会向左旋方向扭转主轴。然而,人类主轴只表现出轻微的全球扭曲，提出了这些分子扭矩如何平衡的问题。这里,使用晶格光片显微镜，我们发现上皮细胞系MCF10A的后期纺锤体具有较高的基线扭曲，我们确定了增加和减少这种扭曲的因素。中区电机KIF4A和MKLP1在后期左旋扭曲需要冗余，我们显示KIF4A在体外产生左手扭矩。肌动蛋白细胞骨架也有助于左手扭曲，但是动力蛋白及其皮质募集因子LGN抵消了它。一起,我们的工作表明，力发生器从主轴内外调节相反方向的扭转，在染色体分离过程中防止强烈的纺锤体扭曲。
