PDF(Pubmed)
Abstract：
Insect wing development is a fascinating and intricate process that involves the regulation of wing size through cell proliferation and apoptosis. In this study, we find that Ter94, an AAA-ATPase, is essential for proper wing size dependently on its ATPase activity. Loss of Ter94 enables the suppression of Hippo target genes. When Ter94 is depleted, it results in reduced wing size and increased apoptosis, which can be rescued by inhibiting the Hippo pathway. Biochemical experiments reveal that Ter94 reciprocally binds to Mer, a critical upstream component of the Hippo pathway, and disrupts its interaction with Ex and Kib. This disruption prevents the formation of the Ex-Mer-Kib complex, ultimately leading to the inactivation of the Hippo pathway and promoting proper wing development. Finally, we show that hVCP, the human homolog of Ter94, is able to substitute for Ter94 in modulating Drosophila wing size, underscoring their functional conservation. In conclusion, Ter94 plays a positive role in regulating wing size by interfering with the Ex-Mer-Kib complex, which results in the suppression of the Hippo pathway.
摘要：
昆虫翅膀的发育是一个迷人而复杂的过程，涉及通过细胞增殖和凋亡调节翅膀大小。在这项研究中,我们发现Ter94是一种AAA-ATP酶,对于适当的机翼大小至关重要，这取决于其ATPase活性。Ter94的缺失能够抑制Hippo靶基因。当Ter94耗尽时，它导致机翼尺寸减小和细胞凋亡增加，可以通过抑制河马途径来拯救。生化实验表明，Ter94与Mer相互结合，河马途径的一个关键上游部分，破坏了它与Ex和Kib的互动.这种破坏阻止了Ex-Mer-Kib复合体的形成，最终导致河马途径失活并促进机翼的正常发育。最后,我们展示了hVCP，Ter94的人类同源物能够代替Ter94调节果蝇的翅膀大小，强调它们的功能保护。总之,Ter94通过干扰Ex-Mer-Kib复合体在调节机翼大小方面发挥着积极作用，这导致河马途径的抑制。
