通过蛋白酶Hayan和Persephone调解的损害感知,用于灭缺陷的中Toll通路的激活
Shotaro Nakano1, Soshiro Kashio1, Kei Nishimura1
1Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
PLoS genetics
|June 15, 2023
概括
在Drosophila中,先天免疫系统损伤的感知涉及到激素蛋白酶 (SPs) 激活托尔通路. 这项研究表明,反应性氧物种 (ROS) 信号损伤,激活了像Persephone (Psh) 这样的SPs来分裂Spätzle (Spz).
科学领域:
- 具有天生的免疫力.
- 损害感应的分子机制 感应损害的分子机制
- 德洛索菲拉 (Drosophila melanogaster) 作为一个模型生物体
背景情况:
- 天生的免疫系统利用血清蛋白酶 (SP) 级联来感知组织损伤并启动无菌免疫反应.
- 在Drosophila中,Toll通路是由组织损伤激活的,需要细胞外SP级联来分裂和激活Toll连接体Spätzle (Spz).
- 虽然Spätzle处理酶 (SPE),Hayan和Persephone (Psh) 在感染中的作用已知,但它们在损伤诱导的Toll激活中的特定作用和上游激活剂仍然不清楚.
研究的目的:
- 为了阐明在Drosophila的组织损伤引起的无菌Toll通路激活期间参与Spz激活的特定SPs.
- 识别与损伤相关的分子,可以在无菌免疫的背景下激活SPs.
- 调查反应性氧物种 (ROS) 在中介损伤诱导的SP激活和通道信号传输中的作用.
主要方法:
- 生产和利用不可食用的spz突变来评估在通道激活时spz裂变的要求.
- 血淋巴的蛋白质组学分析以确定涉及Spz裂变的潜在SPs.
- 使用Drosophila Schneider 2 (S2) 细胞进行实验,以表征SP活动和信号通路,包括基因分析和用过氧化进行功能分析.
主要成果:
- 在应对亡缺陷翅膀表皮损伤时,Spz裂变对于Toll通路的无菌激活至关重要.
- 无论是SPE还是Melanization Protease 1 (MP1),都对Spz裂变具有很高的能力,MP1在S2细胞中作用于Hayan和Psh的下游.
- 哈扬和Psh有助于无菌Toll激活,虽然SPE/MP1双突变在感染时显示Toll激活受损,但在损伤场景中没有消除,这表明涉及其他SP.
- 过氧化在过度表达S2细胞中直接激活Psh-Spz级联,在受损的翅膀中检测到ROS.
结论:
- 哈扬和Psh可能会感觉到死体损伤,并通过SPE和MP1不同的SP启动Spz裂变.
- 反应性氧物种 (ROS) 作为关键的损伤相关信号分子,可以激活SPs,如Psh,从而激活通道.
- 这项研究揭示了先天性免疫感应的新机制,其中ROS作为损伤信号,触发SP介导的免疫激活.
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