Lic regulates JNK-mediated cell death in Drosophila
Lic regulates JNK-mediated cell death in Drosophila
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Lic 调节果蝇 JNK 介导的细胞死亡
DOI：
10.1111/cpr.12593
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发表时间：
2019
影响因子：
8.5
通讯作者：
Xue Lei
中科院分区：
文献类型：
--
作者：
Sun Yihao;Zhang Di;Li Chenglin;Huang Jiuhong;Li Wenzhe;Qiu Yu;Mao Aiwu;Zhou Mingcheng;Xue Lei
目的JNK信号通路在细胞死亡中起着重要作用，但调控该信号通路的因素尚未完全揭示。在这项研究中，我们的目的是确定额外的因素，调节JNK信号在细胞死亡，并表征潜在mechanism.Materials和MethodsDrosophila提出了标准培养基，并在25°C进行交叉。Gal 4/UAS系统用于以特定的时间和空间模式表达蛋白质或RNAi。通过GFP荧光、X-gal染色或3龄幼虫眼和翅盘的免疫染色揭示基因表达。通过吖啶橙子（AO）染色观察细胞死亡。果蝇眼睛和翅膀的图像由OLYMPUS显微镜拍摄。结果我们发现，编码果蝇MKK 3的独角兽（lic）是JNK介导的细胞死亡的重要调节因子。首先，flc的缺失抑制了眼和翅膀发育中异位Egr触发的JNK激活和细胞死亡。其次，在翅膀发育中，细胞极性丧失诱导的生理性JNK依赖性细胞死亡是必需的。第三，Lic过表达足以在发育中的眼睛和翅膀中启动JNK介导的细胞死亡。此外，异位Lic通过促进JNK磷酸化激活JNK信号传导。最后，遗传上位性分析证实Lic与Hep在Egr‐JNK pathway.ConclusionsThis study not only identified Lic as a novel component of the JNK signaling，but also discussed the critical roles and mechanism of Lic in cell death.
ObjectivesThe evolutionary conserved JNK pathway plays crucial role in cell death, yet factors that modulate this signalling have not been fully disclosed. In this study, we aim to identify additional factors that regulate JNK signalling in cell death, and characterize the underlying mechanisms.Materials and MethodsDrosophilawere raised on standard media, and cross was carried out at 25°C. The Gal4/UAS system was used to express proteins or RNAi in a specific temporal and spatial pattern. Gene expression was revealed by GFP fluorescence, X‐gal staining or immunostaining of 3rd instar larval eye and wing discs. Cell death was visualized by acridine orange (AO) staining. Images of fly eyes and wings were taken by OLYMPUS microscopes.ResultsWe found thatlicorne(lic) encoding theDrosophilaMKK3 is an essential regulator of JNK‐mediated cell death. Firstly, loss oflicsuppressed ectopic Egr‐triggered JNK activation and cell death in eye and wing development. Secondary,licis necessary for loss‐of‐cell polarity‐induced, physiological JNK‐dependent cell death in wing development. Thirdly, Lic overexpression is sufficient to initiate JNK‐mediated cell death in developing eyes and wings. Furthermore, ectopic Lic activates JNK signalling by promoting JNK phosphorylation. Finally, genetic epistatic analysis confirmed that Lic acts in parallel with Hep in the Egr‐JNK pathway.ConclusionsThis study not only identified Lic as a novel component of the JNK signalling, but also disclosed the crucial roles and mechanism of Lic in cell death.