A Hippo-like Signaling Pathway Controls Tracheal Morphogenesis in Drosophila melanogaster.
A Hippo-like Signaling Pathway Controls Tracheal Morphogenesis in Drosophila melanogaster.
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DOI：
10.1016/j.devcel.2018.09.024
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发表时间：
2018-12-03
影响因子：
11.8
通讯作者：
Harvey KF
中科院分区：
文献类型：
--
作者：
Poon CLC;Liu W;Song Y;Gomez M;Kulaberoglu Y;Zhang X;Xu W;Veraksa A;Hergovich A;Ghabrial A;Harvey KF
海马样通路是最早在酵母中发现的古老信号模块。最好定义的后生动物模块形成了Hippo通路的核心，该通路调节器官大小和细胞命运。河马样激酶模块由无菌20样激酶、NDR激酶和非催化蛋白质支架组成。在Hippo途径中，上游激酶Hippo可以被另一种激酶Tao-1激活。在这里，我们描绘了一个相关的海马样信号转导模块，陶-1调节控制果蝇气管形态发生。Tao-1通过磷酸化其激活环来激活Sterile 20样激酶GckIII，这是一种在人类中保守的调节模式。Tao-1和GckIII作用于NDR激酶Tricornered的上游，以确保气管中正确的管形成。我们的研究表明，Tao-1激活两个相关的激酶模块来控制生长和形态发生。我们所描绘的海马样信号通路在人类血管疾病脑海绵状血管畸形中具有潜在的作用。Poon等人，描述了包括激酶Tao-1、GckIII和Tricornered的Hippo样信号通路的发现，及其在果蝇中的气管形态发生中的作用。这些发现增强了我们对管形成的理解，并有可能为人类血管疾病脑海绵状血管畸形提供见解。
Hippo-like pathways are ancient signalling modules first identified in yeasts. The best-defined metazoan module forms the core of the Hippo pathway, which regulates organ size and cell fate. Hippo-like kinase modules consist of a Sterile 20-like kinase, an NDR kinase and non-catalytic protein scaffolds. In the Hippo pathway, the upstream kinase Hippo can be activated by another kinase, Tao-1. Here, we delineate a related Hippo-like signalling module that Tao-1 regulates to control tracheal morphogenesis in Drosophila melanogaster. Tao-1 activates the Sterile 20-like kinase GckIII by phosphorylating its activation loop, a mode of regulation that is conserved in humans. Tao-1 and GckIII act upstream of the NDR kinase Tricornered to ensure proper tube formation in trachea. Our study reveals that Tao-1 activates two related kinase modules to control both growth and morphogenesis. The Hippo-like signalling pathway we have delineated has a potential role in the human vascular disease cerebral cavernous malformation. Poon et al., describe the discovery of a Hippo-like signaling pathway comprising the kinases Tao-1, GckIII and Tricornered, and its role in tracheal morphogenesis in Drosophila. These discoveries enhance our understanding of tube formation, and have the potential to offer insights into the human vascular disease cerebral cavernous malformation.
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