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活性氧激活果蝇 TNF 受体 Wengen 以促进损伤诱导的再生。

Reactive oxygen species activate the Drosophila TNF receptor Wengen for damage-induced regeneration.

机构信息

Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain.

Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.

出版信息

EMBO J. 2024 Sep;43(17):3604-3626. doi: 10.1038/s44318-024-00155-9. Epub 2024 Jul 17.

DOI:10.1038/s44318-024-00155-9
PMID:39020149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11377715/
Abstract

Tumor necrosis factor receptors (TNFRs) control pleiotropic pro-inflammatory functions that range from apoptosis to cell survival. The ability to trigger a particular function will depend on the upstream cues, association with regulatory complexes, and downstream pathways. In Drosophila melanogaster, two TNFRs have been identified, Wengen (Wgn) and Grindelwald (Grnd). Although several reports associate these receptors with JNK-dependent apoptosis, it has recently been found that Wgn activates a variety of other functions. We demonstrate that Wgn is required for survival by protecting cells from apoptosis. This is mediated by dTRAF1 and results in the activation of p38 MAP kinase. Remarkably, Wgn is required for apoptosis-induced regeneration and is activated by the reactive oxygen species (ROS) produced following apoptosis. This ROS activation is exclusive for Wgn, but not for Grnd, and can occur after knocking down Eiger/TNFα. The extracellular cysteine-rich domain of Grnd is much more divergent than that of Wgn, which is more similar to TNFRs from other animals, including humans. Our results show a novel TNFR function that responds to stressors by ensuring p38-dependent regeneration.

摘要

肿瘤坏死因子受体 (TNFRs) 控制着多种促炎功能，范围从细胞凋亡到细胞存活。触发特定功能的能力将取决于上游线索、与调节复合物的关联以及下游途径。在黑腹果蝇中，已经鉴定出两种 TNFR，Wengen (Wgn) 和 Grindelwald (Grnd)。尽管有几项报告将这些受体与 JNK 依赖性细胞凋亡联系起来，但最近发现 Wgn 激活了多种其他功能。我们证明 Wgn 通过保护细胞免受凋亡来维持细胞存活。这是通过 dTRAF1 介导的，导致 p38 MAP 激酶的激活。值得注意的是，Wgn 对于凋亡诱导的再生是必需的，并且在凋亡后产生的活性氧物质 (ROS) 的作用下被激活。这种 ROS 激活是 Wgn 所特有的，而不是 Grnd 所特有的，并且可以在敲低 Eiger/TNFα 后发生。Grnd 的细胞外富含半胱氨酸的结构域比 Wgn 的结构域更加多样化，Wgn 的结构域与其他动物（包括人类）的 TNFR 更相似。我们的结果显示了一种新的 TNFR 功能，它通过确保 p38 依赖性再生来应对应激源。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/11377715/f7bcf14aaf99/44318_2024_155_Fig9_ESM.jpg
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本文引用的文献

1
Drosophila TNF/TNFRs: At the crossroad between metabolism, immunity, and tissue homeostasis.果蝇肿瘤坏死因子/肿瘤坏死因子受体：处于代谢、免疫和组织稳态的交叉点
FEBS Lett. 2023 Oct;597(19):2416-2432. doi: 10.1002/1873-3468.14716. Epub 2023 Aug 26.
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The Drosophila tumor necrosis factor receptor, Wengen, couples energy expenditure with gut immunity.果蝇肿瘤坏死因子受体 Wengen 将能量消耗与肠道免疫联系起来。
Sci Adv. 2023 Jun 9;9(23):eadd4977. doi: 10.1126/sciadv.add4977.
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Actin remodeling mediates ROS production and JNK activation to drive apoptosis-induced proliferation.
肌动蛋白重构介导 ROS 产生和 JNK 激活，以驱动凋亡诱导的增殖。
PLoS Genet. 2022 Dec 5;18(12):e1010533. doi: 10.1371/journal.pgen.1010533. eCollection 2022 Dec.
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The sooner, the better: ROS, kinases and nutrients at the onset of the damage response in .越快越好：活性氧、激酶与损伤反应起始时的营养物质
Front Cell Dev Biol. 2022 Oct 24;10:1047823. doi: 10.3389/fcell.2022.1047823. eCollection 2022.
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Nutrition and PI3K/Akt signaling are required for p38-dependent regeneration.营养和 PI3K/Akt 信号通路对于依赖于 p38 的再生是必需的。
Development. 2021 Apr 15;148(8). doi: 10.1242/dev.197087. Epub 2021 Apr 23.
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Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation.交互式生命树 (iTOL) v5：一个用于显示和注释系统发育树的在线工具。
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Drosophila TNFRs Grindelwald and Wengen bind Eiger with different affinities and promote distinct cellular functions.果蝇 TNFRs Grindelwald 和 Wengen 以不同的亲和力结合 Eiger，并促进不同的细胞功能。
Nat Commun. 2021 Apr 6;12(1):2070. doi: 10.1038/s41467-021-22080-9.
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Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects.肿瘤坏死因子受体：多效性信号复合物及其差异效应
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Basement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue.ROS 和 JNK 介导线粒体膜损伤导致 MMP2 激活，从而驱动巨噬细胞募集到过度生长的组织中。
Nat Commun. 2020 Jul 20;11(1):3631. doi: 10.1038/s41467-020-17399-8.
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A Cambrian-Ordovician Terrestrialization of Arachnids.蛛形纲动物的寒武纪 - 奥陶纪陆地化
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