Epithelial cell shape is regulated by Lulu proteins via myosin-II
Epithelial cell shape is regulated by Lulu proteins via myosin-II
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DOI：
10.1242/jcs.057752
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发表时间：
2010-02-15
影响因子：
4
通讯作者：
Tanoue, Takuji
中科院分区：
文献类型：
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作者：
Nakajima, Hiroyuki;Tanoue, Takuji
上皮结构中的细胞形状变化是动物形态发生的基础。最近的研究确定肌球蛋白-II作为形态发生过程中细胞形状变化的驱动力的主要发生器。Lulu（Epb 41 l5）是形态发生的主要调节因子，尽管哺乳动物中下游分子和细胞机制仍然不清楚。在果蝇和斑马鱼中，Lulu蛋白被报道负调节Crumbs，一种顶端结构域调节剂，从而调节形态发生。在这项研究中，我们发现哺乳动物Lulu激活肌球蛋白II，从而调节上皮细胞的形状。在我们的实验中，Lulu在上皮细胞中的表达导致细胞的顶端收缩和侧向伸长，伴随着肌球蛋白II的上调。肌球蛋白-II活性的抑制几乎完全阻断了这种Lulu驱动的细胞形状变化。我们进一步发现Rock参与了肌球蛋白II的激活。此外，RNAi介导的上皮细胞中Lulu的耗竭导致肌球蛋白II的解体和细胞中适当的侧向结构域组织的伴随损失。从这些结果，我们建议，露露调节上皮细胞的形状，通过控制肌球蛋白-II的活性。
Cell-shape change in epithelial structures is fundamental to animal morphogenesis. Recent studies identified myosin-II as the major generator of driving forces for cell-shape changes during morphogenesis. Lulu (Epb41l5) is a major regulator of morphogenesis, although the downstream molecular and cellular mechanisms remain obscure in mammals. In Drosophila and zebrafish, Lulu proteins were reported to negatively regulate Crumbs, an apical domain regulator, thus regulating morphogenesis. In this study, we show that mammalian Lulu activates myosin-II, thus regulating epithelial cell shape. In our experiments, Lulu expression in epithelial cells resulted in apical constriction and lateral elongation in the cells, accompanied by upregulation of myosin-II. The inhibition of myosin-II activity almost completely blocked this Lulu-driven cell-shape change. We further found that Rock participates in the myosin-II activation. Additionally, RNAi-mediated depletion of Lulu in epithelial cells resulted in disorganization of myosin-II and a concomitant loss of proper lateral domain organization in the cells. From these results, we propose that Lulu regulates epithelial cell shape by controlling myosin-II activity.