Moesin controls cortical rigidity, cell rounding, and spindle morphogenesis during mitosis
Moesin controls cortical rigidity, cell rounding, and spindle morphogenesis during mitosis
复制标题
DOI：
10.1016/j.cub.2007.12.051
复制
发表时间：
2008-01-22
期刊：
影响因子：
9.2
通讯作者：
Baum, Buzz
中科院分区：
文献类型：
--
作者：
Kunda, Patricia;Pelling, Andrew E.;Baum, Buzz
背景资料：在有丝分裂过程中，动物细胞经历一系列复杂的形态学变化，从有丝分裂开始时的细胞边缘收缩和细胞变圆到有丝分裂退出时的轴向伸长和胞质分裂。然而，驱动有丝分裂细胞形态早期变化的分子机制及其功能意义仍然未知。在这里，我们确定Moesin作为一个关键的球员。膜突蛋白是唯一的果蝇成员的ERM蛋白，其中，一旦激活通过磷酸化，交联肌动蛋白丝的细胞质尾巴的质膜protein.Results：我们发现，膜突蛋白被激活后进入有丝分裂，是必要的伴随增加皮质硬度和细胞圆化，人工激活时，足以诱导这两个过程中的间期细胞，独立的肌球蛋白II。这种磷酸化Moesin诱导的皮质硬度增加在有丝分裂过程中起着重要作用，因为纺锤体形态发生和染色体排列在Moesin RNAi细胞中受到损害。然而，值得注意的是，在软中期细胞中观察到的纺锤体缺陷可以通过从细胞外重建皮质张力来挽救。这些数据表明，伴随有丝分裂进程的膜突蛋白的活性和定位的变化有助于建立刚性的，圆形皮质在中期和极性松弛在后期，并揭示了这种Moesin的重要性，诱导皮层硬度增加，纺锤体形态建成和染色体分离有序。在这样做的过程中，它们有助于解释为什么皮层结构的动态变化是动物细胞有丝分裂的普遍特征。
Background: During mitosis, animal cells undergo a complex sequence of morphological changes, from retraction of the cell margin and cell rounding at the onset of mitosis to axial elongation and cytokinesis at mitotic exit. The molecular mechanisms driving the early changes in mitotic cell form and their functional significance, however, remain unknown. Here we identify Moesin as a key player. Moesin is the sole Drosophila member of the ERM proteins, which, once activated via phosphorylation, crosslink actin filaments to the cytoplasmic tails of plasma membrane proteins.Results: We find that the Moesin is activated upon entry into mitosis, is necessary for the accompanying increase in cortical rigidity and cell rounding and, when artificially activated, is sufficient to induce both processes in interphase cells, independently of Myosin II. This phospho-Moesin-induced increase in cortical rigidity plays an important role during mitotic progression, because spindle morphogenesis and chromosome alignment are compromised in Moesin RNAi cells. Significantly, however, the spindle defects observed in soft metaphase cells can be rescued by the re-establishment of cortical tension from outside the cell.Conclusions: These data show that changes in the activity and localization of Moesin that accompany mitotic progression contribute to the establishment of a stiff, rounded cortex at metaphase and to polar relaxation at anaphase and reveal the importance of this Moesin-induced increase in cortical rigidity for spindle morphogenesis and orderly chromosome segregation. In doing so, they help to explain why dynamic changes in cortical architecture are a universal feature of mitosis in animal cells.