Membrane Traffic and Cell Division Laboratory, Institut Pasteur, 75015 Paris, France Centre National de la Recherche Scientifique URA2582, 75015 Paris, France Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Institut de formation doctorale, 75252 Paris, France.
Institut de Biologie de L'Ecole Normale Supérieure, Ecole Normale Supérieure, 75005 Paris, France Institut National de la Santé et de la Recherche Médicale, U1024, Centre National de la Recherche Scientifique UMR8197, 75005 Paris, France.
J Cell Biol. 2014 Jun 23;205(6):791-9. doi: 10.1083/jcb.201401049.
Mitotic spindle orientation relies on a complex dialog between the spindle microtubules and the cell cortex, in which F-actin has been recently implicated. Here, we report that the membrane-actin linkers ezrin/radixin/moesin (ERMs) are strongly and directly activated by the Ste20-like kinase at mitotic entry in mammalian cells. Using microfabricated adhesive substrates to control the axis of cell division, we found that the activation of ERMs plays a key role in guiding the orientation of the mitotic spindle. Accordingly, impairing ERM activation in apical progenitors of the mouse embryonic neocortex severely disturbed spindle orientation in vivo. At the molecular level, ERM activation promotes the polarized association at the mitotic cortex of leucine-glycine-asparagine repeat protein (LGN) and nuclear mitotic apparatus (NuMA) protein, two essential factors for spindle orientation. We propose that activated ERMs, together with Gαi, are critical for the correct localization of LGN-NuMA force generator complexes and hence for proper spindle orientation.
有丝分裂纺锤体的取向依赖于纺锤体微管和细胞皮层之间的复杂对话，最近有研究表明 F-肌动蛋白也参与其中。在这里，我们报告说，在有丝分裂进入时，膜肌动蛋白连接蛋白 ezrin/radixin/moesin（ERM）被 Ste20 样激酶强烈且直接激活。我们使用微制造的粘附基板来控制细胞分裂的轴，发现 ERM 的激活在指导有丝分裂纺锤体的取向中起着关键作用。因此，在小鼠胚胎新皮层的顶端祖细胞中，ERM 激活的损害严重扰乱了体内纺锤体的取向。在分子水平上，ERM 激活促进了亮氨酸-甘氨酸-天冬酰胺重复蛋白 (LGN) 和核有丝分裂装置 (NuMA) 蛋白在有丝分裂皮质的极化结合，这两种蛋白是纺锤体取向所必需的。我们提出，激活的 ERM 与 Gαi 一起，对于 LGN-NuMA 力发生器复合物的正确定位以及纺锤体的正确取向至关重要。
