The ZO-1 protein Polychaetoid as an upstream regulator of the Hippo pathway in Drosophila.
The ZO-1 protein Polychaetoid as an upstream regulator of the Hippo pathway in Drosophila.
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DOI：
10.1371/journal.pgen.1009894
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发表时间：
2021-11
期刊：
影响因子：
4.5
通讯作者：
Xie B
中科院分区：
文献类型：
--
作者：
Sang Q;Wang G;Morton DB;Wu H;Xie B
具有不同光谱灵敏度的光感受器（PR）亚型的多样性对动物的色觉至关重要。在果蝇的眼睛中，Hippo通路与蓝色和绿色敏感的PR亚型命运规范有关。具体来说，Hippo通路的激活促进了绿色敏感PR的命运，而牺牲了蓝色敏感PR的命运。在这里，我们使用一种基于三杂合子的增敏遗传筛选方法，报道了在蓝绿敏感的PR亚型二元命运选择过程中，单个果蝇zonula occludens-1 （ZO-1）蛋白Polychaetoid （Pyd）作为Hippo通路的新调节剂的鉴定。我们证明Pyd作用于Hippo通路的上游核心成分和上游调节因子Pez。此外，我们发现Pyd抑制Su（dx）的活性，Su（dx）是一种负调控Pez的E3连接酶，可以在PR亚型命运规范期间与Pyd物理相互作用。总之，我们的研究结果确定了Hippo信号通路在有丝分裂后神经元命运规范中的新机制。Hippo信号通路最初是因其在组织生长和器官大小控制中的关键作用而被发现的。它在多种生物过程中的进化保守作用，包括细胞分化、干细胞再生和稳态、先天免疫生物学以及肿瘤发生，随后在其他物种中被发现。在果蝇眼睛的发育过程中，Hippo通路促进绿色和抑制蓝色敏感光感受器（PR）亚型命运规范。利用这种二元PR命运选择，我们筛选果蝇染色体缺陷系以寻找新的Hippo信号通路调节因子。我们发现果蝇膜相关的ZO-1蛋白Pyd是Hippo途径的上游调节剂，可以指定PR亚型。我们的研究结果表明，Pyd抑制Su（dx）在Hippo通路中的活性，从而指定PR亚型。我们的研究结果证明了Hippo信号通路在有丝分裂后神经元命运规范中的新机制。
The generation of a diversity of photoreceptor (PR) subtypes with different spectral sensitivities is essential for color vision in animals. In the Drosophila eye, the Hippo pathway has been implicated in blue- and green-sensitive PR subtype fate specification. Specifically, Hippo pathway activation promotes green-sensitive PR fate at the expense of blue-sensitive PRs. Here, using a sensitized triple heterozygote-based genetic screening approach, we report the identification of the single Drosophila zonula occludens-1 (ZO-1) protein Polychaetoid (Pyd) as a new regulator of the Hippo pathway during the blue- and green-sensitive PR subtype binary fate choice. We demonstrate that Pyd acts upstream of the core components and the upstream regulator Pez in the Hippo pathway. Furthermore, We found that Pyd represses the activity of Su(dx), a E3 ligase that negatively regulates Pez and can physically interact with Pyd, during PR subtype fate specification. Together, our results identify a new mechanism underlying the Hippo signaling pathway in post-mitotic neuronal fate specification. The Hippo signaling pathway was originally discovered for its critical role in tissue growth and organ size control. Its evolutionarily conserved roles in various biological processes, including cell differentiation, stem cell regeneration and homeostasis, innate immune biology, as well as tumorigenesis, have been subsequently found in other species. During the development of the Drosophila eye, the Hippo pathway promotes green- and represses blue-sensitive photoreceptor (PR) subtype fate specification. Taking advantage of this binary PR fate choice, we screened Drosophila chromosomal deficiency lines to seek new regulators of the Hippo signaling pathway. We identified the Drosophila membrane-associated ZO-1 protein Pyd as an upstream regulator of the Hippo pathway to specify PR subtypes. Our results have demonstrated that Pyd represses Su(dx)’s activity in the Hippo pathway to specify PR subtypes. Our results demonstrate a new mechanism underlying the Hippo signaling pathway in post-mitotic neuronal fate specification.
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DOI：
10.1126/science.1199010
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Heallen T;Zhang M;Wang J;Bonilla-Claudio M;Klysik E;Johnson RL;Martin JF
通讯作者：
Martin JF
影响因子：
16.2
作者：
Chou, WH;Hall, KJ;Britt, SG
通讯作者：
Britt, SG
影响因子：
12.3
作者：
Cook RK;Christensen SJ;Deal JA;Coburn RA;Deal ME;Gresens JM;Kaufman TC;Cook KR
通讯作者：
Cook KR
影响因子：
64.5
作者：
Freeman, M
通讯作者：
Freeman, M
影响因子：
9.2
作者：
Bennett, F. Christian;Harvey, Kieran F.
通讯作者：
Harvey, Kieran F.