Aurora A Triggers Lgl Cortical Release during Symmetric Division to Control Planar Spindle Orientation
Aurora A Triggers Lgl Cortical Release during Symmetric Division to Control Planar Spindle Orientation
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DOI：
10.1016/j.cub.2014.10.053
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发表时间：
2015-01-05
期刊：
影响因子：
9.2
通讯作者：
Morais-de-Sa, Eurico
中科院分区：
文献类型：
--
作者：
Carvalho, Catia A.;Moreira, Sofia;Morais-de-Sa, Eurico
有丝分裂纺锤体取向对控制细胞命运规范和上皮结构[1]至关重要。肿瘤抑制因子Lgl定位于上皮细胞的基底外侧皮层，在那里它与Dlg和Scrib一起组织顶基底极性[2]。Dlg和Scrib也控制平面主轴方向[3,4]，但如何调整极性配合物的组织来控制对称分裂在很大程度上是未知的。在这里，我们发现在果蝇滤泡上皮细胞分裂过程中，当Lgl被释放到细胞质中时，Dlg复合体被重塑。在上皮细胞有丝分裂过程中，Lgl的重新分配让人想起不对称的细胞分裂，其中提出Aurora A促进aPKC激活以控制Lgl和细胞命运决定因素[5]的定位。我们发现Aurora A直接控制Lgl的定位，在上皮细胞和S2细胞的早期触发其皮质释放。这依赖于假定的aPKC磷酸化位点内的双磷酸化，这是有丝分裂期间Lgl皮质释放所必需和充分的，可以通过aPKC和Aurora a活性的结合来实现。皮质保留的Lgl破坏平面纺锤体取向，但只有当可以结合Dlg的Lgl突变体表达时。因此，我们的工作揭示了Lgl有丝分裂皮层释放与命运决定因素的不对称分离没有特异性联系，我们提出极光A的激活打破了Dlg/Lgl相互作用，从而通过pin (LGN)/Dlg途径在对称分裂过程中允许平面纺锤体定向。
Mitotic spindle orientation is essential to control cell-fate specification and epithelial architecture [1]. The tumor suppressor Lgl localizes to the basolateral cortex of epithelial cells, where it acts together with Dlg and Scrib to organize apicobasal polarity [2]. Dlg and Scrib also control planar spindle orientation [3, 4], but how the organization of polarity complexes is adjusted to control symmetric division is largely unknown. Here, we show that the Dlg complex is remodeled during Drosophila follicular epithelium cell division, when Lgl is released to the cytoplasm. Lgl redistribution during epithelial mitosis is reminiscent of asymmetric cell division, where it is proposed that Aurora A promotes aPKC activation to control the localization of Lgl and cell-fate determinants [5]. We show that Aurora A controls Lgl localization directly, triggering its cortical release at early prophase in both epithelial and S2 cells. This relies on double phosphorylation within the putative aPKC phosphorylation site, which is required and sufficient for Lgl cortical release during mitosis and can be achieved by a combination of aPKC and Aurora A activities. Cortical retention of Lgl disrupts planar spindle orientation, but only when Lgl mutants that can bind Dlg are expressed. Hence, our work reveals that Lgl mitotic cortical release is not specifically linked to the asymmetric segregation of fate determinants, and we propose that Aurora A activation breaks the Dlg/Lgl interaction to allow planar spindle orientation during symmetric division via the Pins (LGN)/Dlg pathway.