Regulation of Lethal giant larvae by Dishevelled
Regulation of Lethal giant larvae by Dishevelled
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DOI：
10.1038/nature04116
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发表时间：
2005-10-27
期刊：
影响因子：
64.8
通讯作者：
Sokol, SY
中科院分区：
文献类型：
--
作者：
Dollar, GL;Weber, U;Sokol, SY
在许多细胞类型中极性的建立依赖于Lgl，一种致命巨型幼虫的肿瘤抑制产物，它参与基底外侧蛋白靶向（1-4）。Par3、Par6和非典型蛋白激酶C5-8的保守复合物使顶端表面的Lgl磷酸化并失活；然而，在发育过程中协调细胞极化的信号传导机制尚未明确。在这里，我们表明Lgl的脊椎动物同源物与Wnt信号传导的重要介质Dishevelled相关，并且Dishevelled调节Lgl在非洲爪蟾外胚层和果蝇滤泡上皮中的定位。我们发现Lgl和Dsh都是爪蟾外胚层细胞正常的顶基极性所必需的。此外，我们发现Wnt受体frizzled8，而不是frizzled7，会导致Lgl与皮层分离，并伴随其在体内的活性丧失。这些发现提示了卷曲和散乱调节细胞极性的分子基础。
The establishment of polarity in many cell types depends on Lgl, the tumour suppressor product of lethal giant larvae, which is involved in basolateral protein targeting(1-4). The conserved complex of Par3, Par6 and atypical protein kinase C5-8 phosphorylates and inactivates Lgl at the apical surface; however, the signalling mechanisms that coordinate cell polarization in development are not well defined. Here we show that a vertebrate homologue of Lgl associates with Dishevelled, an essential mediator of Wnt signalling, and that Dishevelled regulates the localization of Lgl in Xenopus ectoderm and Drosophila follicular epithelium. We show that both Lgl and Dsh are required for normal apical - basal polarity of Xenopus ectodermal cells. In addition, we show that the Wnt receptor Frizzled 8, but not Frizzled 7, causes Lgl to dissociate from the cortex with the concomitant loss of its activity in vivo. These findings suggest a molecular basis for the regulation of cell polarity by Frizzled and Dishevelled.