Levy Jennifer R, Holzbaur Erika L F
Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USA.
J Cell Sci. 2008 Oct 1;121(Pt 19):3187-95. doi: 10.1242/jcs.033878. Epub 2008 Sep 9.
During directed cell migration, the movement of the nucleus is coupled to the forward progression of the cell. The microtubule motor cytoplasmic dynein is required for both cell polarization and cell motility. Here, we investigate the mechanism by which dynein contributes to directed migration. Knockdown of dynein slows protrusion of the leading edge and causes defects in nuclear movements. The velocity of nuclear migration was decreased in dynein knockdown cells, and nuclei were mislocalized to the rear of motile cells. In control cells, we observed that wounding the monolayer stimulated a dramatic induction of nuclear rotations at the wound edge, reaching velocities up to 8.5 degrees/minute. These nuclear rotations were significantly inhibited in dynein knockdown cells. Surprisingly, centrosomes do not rotate in concert with the nucleus; instead, the centrosome remains stably positioned between the nucleus and the leading edge. Together, these results suggest that dynein contributes to migration in two ways: (1) maintaining centrosome centrality by tethering microtubule plus ends at the cortex; and (2) maintaining nuclear centrality by asserting force directly on the nucleus.
在定向细胞迁移过程中，细胞核的运动与细胞的向前推进相关联。微管动力蛋白胞质动力蛋白对于细胞极化和细胞运动都是必需的。在此，我们研究动力蛋白促进定向迁移的机制。敲低动力蛋白会减缓前缘的突出，并导致核运动缺陷。在敲低动力蛋白的细胞中，核迁移速度降低，并且细胞核会错误定位到运动细胞的后部。在对照细胞中，我们观察到损伤单层会刺激伤口边缘的细胞核发生显著的旋转诱导，速度高达每分钟8.5度。这些细胞核旋转在敲低动力蛋白的细胞中受到显著抑制。令人惊讶的是，中心体并不与细胞核协同旋转；相反，中心体稳定地定位在细胞核和前缘之间。总之，这些结果表明动力蛋白以两种方式促进迁移：（1）通过将微管正端拴系在皮质上来维持中心体的中心位置；（2）通过直接对细胞核施加力来维持细胞核的中心位置。
