MRC - Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
MRC - Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK
Development. 2019 Aug 12;146(15):dev175497. doi: 10.1242/dev.175497.
Cdc42 regulates epithelial morphogenesis together with the Par complex (Baz/Par3-Par6-aPKC), Crumbs (Crb/CRB3) and Stardust (Sdt/PALS1). However, how these proteins work together and interact during epithelial morphogenesis is not well understood. To address this issue, we used the genetically amenable pupal photoreceptor and follicular epithelium. We show that during epithelial morphogenesis active Cdc42 accumulates at the developing apical membrane and cell-cell contacts, independently of the Par complex and Crb. However, membrane localization of Baz, Par6-aPKC and Crb all depend on Cdc42. We find that although binding of Cdc42 to Par6 is not essential for the recruitment of Par6 and aPKC to the membrane, it is required for their apical localization and accumulation, which we find also depends on Par6 retention by Crb. In the pupal photoreceptor, membrane recruitment of Par6-aPKC also depends on Baz. Our work shows that Cdc42 is required for this recruitment and suggests that this factor promotes the handover of Par6-aPKC from Baz onto Crb. Altogether, we propose that Cdc42 drives morphogenesis by conferring apical identity, Par-complex assembly and apical accumulation of Crb.
Cdc42 与 Par 复合物(Baz/Par3-Par6-aPKC)、Crb(Crb/CRB3)和 Stardust(Sdt/PALS1)一起调节上皮形态发生。然而,这些蛋白质在上皮形态发生过程中是如何协同作用和相互作用的还不是很清楚。为了解决这个问题,我们使用了遗传上易于操作的蛹期光感受器和滤泡上皮。我们表明,在上皮形态发生过程中,活性 Cdc42 积累在发育中的顶膜和细胞-细胞接触处,这与 Par 复合物和 Crb 无关。然而,Baz、Par6-aPKC 和 Crb 的膜定位都依赖于 Cdc42。我们发现,尽管 Cdc42 与 Par6 的结合对于 Par6 和 aPKC 到膜的募集不是必需的,但它对于它们的顶端定位和积累是必需的,我们发现这也依赖于 Crb 对 Par6 的保留。在蛹期光感受器中,Par6-aPKC 的膜募集也依赖于 Baz。我们的工作表明,Cdc42 是这种募集所必需的,并表明该因子促进了 Par6-aPKC 从 Baz 到 Crb 的交接。总之,我们提出 Cdc42 通过赋予顶膜特性、Par 复合物组装和 Crb 的顶端积累来驱动形态发生。