Shaggy regulates tissue growth through Hippo pathway in Drosophila
Shaggy regulates tissue growth through Hippo pathway in Drosophila
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Shaggy 通过 Hippo 途径调节果蝇的组织生长
DOI：
10.1007/s11427-022-2156-2
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发表时间：
2022-09-01
影响因子：
9.1
通讯作者：
Jiao，Renjie
中科院分区：
文献类型：
--
作者：
Wu，Honggang;Zhu，Nannan;Jiao，Renjie
进化上保守的Hippo途径协调细胞增殖、分化和凋亡以调节器官生长和肿瘤发生。Hippo信号传导活性受到包括生长因子和细胞极性在内的各种上游信号的严格控制，但该途径在发育过程中受到调节的程度仍有待解决。在这里，我们报告了Shaggy的鉴定，哺乳动物GSK 3 β的同源物，作为果蝇中Hippo通路的一种新的调节剂。我们的研究结果表明，Shaggy以依赖于其激酶活性的方式促进Hippo靶基因的表达。Shaggy的缺失导致Yorkie抑制和Hippo途径靶基因的下调。从机制上讲，Shaggy作用于Hippo通路的上游，并负调节含有接头蛋白Expanded的FERM结构域的丰度。我们的研究结果表明，Shaggy在功能上是Crumbs/Slmbs介导的Expandedin体内下调所必需的，这在细胞结构和Hippo信号通路之间提供了潜在的分子联系。
The evolutionarily conserved Hippo pathway coordinates cell proliferation, differentiation and apoptosis to regulate organ growth and tumorigenesis. Hippo signaling activity is tightly controlled by various upstream signals including growth factors and cell polarity, but the full extent to which the pathway is regulated during development remains to be resolved. Here, we report the identification of Shaggy, the homolog of mammalian Gsk3β, as a novel regulator of the Hippo pathway inDrosophila. Our results show that Shaggy promotes the expression of Hippo target genes in a manner that is dependent on its kinase activity. Loss of Shaggy leads to Yorkie inhibition and downregulation of Hippo pathway target genes. Mechanistically, Shaggy acts upstream of the Hippo pathway and negatively regulates the abundance of the FERM domain containing adaptor protein Expanded. Our results reveal that Shaggy is functionally required for Crumbs/Slmb-mediated downregulation of Expandedin vivo, providing a potential molecular link between cellular architecture and the Hippo signaling pathway.