C‐terminal–mediated homodimerization of Expanded is critical for its ability to promote Hippo signalling in Drosophila
C‐terminal–mediated homodimerization of Expanded is critical for its ability to promote Hippo signalling in Drosophila
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DOI：
10.1002/1873-3468.14332
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发表时间：
2022-03
期刊：
影响因子：
3.5
通讯作者：
Guiping Wang;Chaojun Zhai;Xiaohui Ji;Enlin Wang;Shanshan Zhao;Chenxi Qian;Dongyue Yu;Yunfeng Wang;Shian Wu
中科院分区：
文献类型：
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作者：
Guiping Wang;Chaojun Zhai;Xiaohui Ji;Enlin Wang;Shanshan Zhao;Chenxi Qian;Dongyue Yu;Yunfeng Wang;Shian Wu
Hippo信号在组织生长和稳态中起关键作用，其失调与多种人类疾病有关。Expanded（Ex）是Hippo信号传导的重要上游激活剂;然而，Ex如何激活Hippo信号传导仍然知之甚少。在这里，我们证明了Ex通过C末端相互作用形成同源二聚体，并且ExC 2区域（912-1164 aa）对于Ex二聚化是足够的和必需的。功能分析表明，ExC 2是Ex促进果蝇细胞中Yki磷酸化和失活所必需的。进一步的体内分析表明ExC 2对于Ex控制果蝇组织生长是重要的。因此，我们的研究揭示了一种新的机制，即Ex同源二聚化介导其完全激活，以促进生长控制中的Hippo信号传导。
Hippo signalling plays key role in tissue growth and homeostasis, and its dysregulation is implicated in various human diseases. Expanded (Ex) is an important upstream activator of Hippo signalling; however, how Ex activates Hippo signalling is still poorly understood. Here, we demonstrate that Ex forms a homodimer via C‐terminal interaction, and that the ExC2 region (912–1164 aa) is sufficient and essential for Ex dimerization. Functional analysis shows that ExC2 is required for Ex to promote the phosphorylation and inactivation of Yki in Drosophila cells. Further in vivo analysis shows that ExC2 is important for Ex to control Drosophila tissue growth. Our study, thus, uncovers a novel mechanism whereby Ex homodimerization mediates its full activation to promote Hippo signalling in growth control.