Tame Mihoko A, Raaijmakers Jonne A, van den Broek Bram, Lindqvist Arne, Jalink Kees, Medema René H
Division of Cell Biology; The Netherlands Cancer Institute; Amsterdam, The Netherlands.
Department of Cell and Molecular Biology; Karolinska Institutet; Stockholm, Sweden.
Cell Cycle. 2014;13(7):1162-70. doi: 10.4161/cc.28031. Epub 2014 Feb 10.
Cytoplasmic dynein is recruited to the cell cortex in early mitosis, where it can generate pulling forces on astral microtubules to position the mitotic spindle. Recent work has shown that dynein displays a dynamic asymmetric cortical localization, and that dynein recruitment is negatively regulated by spindle pole-proximity. This results in oscillating dynein recruitment to opposite sides of the cortex to center the mitotic spindle. However, although the centrosome-derived signal that promotes displacement of dynein has been identified, it is currently unknown how dynein is re-recruited to the cortex once it has been displaced. Here we show that re-recruitment of cortical dynein requires astral microtubules. We find that microtubules are necessary for the sustained localized enrichment of dynein at the cortex. Furthermore, we show that stabilization of astral microtubules causes spindle misorientation, followed by mispositioning of dynein at the cortex. Thus, our results demonstrate the importance of astral microtubules in the dynamic regulation of cortical dynein recruitment in mitosis.
细胞质动力蛋白在有丝分裂早期被招募到细胞皮层,在那里它可以在星体微管上产生拉力以定位有丝分裂纺锤体。最近的研究表明,动力蛋白表现出动态不对称的皮层定位,并且动力蛋白的招募受到纺锤体极接近程度的负调控。这导致动力蛋白在皮层的相对两侧振荡招募,以使有丝分裂纺锤体居中。然而,尽管已经确定了促进动力蛋白移位的中心体衍生信号,但目前尚不清楚动力蛋白一旦被移位后如何重新被招募到皮层。在这里,我们表明皮层动力蛋白的重新招募需要星体微管。我们发现微管对于动力蛋白在皮层的持续局部富集是必要的。此外,我们表明星体微管的稳定会导致纺锤体定向错误,随后动力蛋白在皮层的定位错误。因此,我们的结果证明了星体微管在有丝分裂中皮层动力蛋白招募的动态调节中的重要性。