由于其域混合起源,IL-17途径与神经和TLR/IL-1R途径交织在一起
Shenghui Chen1,2, Huiping Fan1, Chenrui Ran1
1State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
概括
IL-17途径通过域混合进化,并与其祖先途径保持联系,在动物血统中驱动各种功能. 这种进化相互作用解释了它的各种角色和操纵潜力.
科学领域:
- 进化生物学是进化的生物学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 介素-17 (IL-17) 途径在动物种群中表现出显著的功能多样性,但进化驱动因素仍然不清楚.
- 了解IL-17通路的起源对于破译它在免疫和发育中的多种作用至关重要.
研究的目的:
- 研究IL-17路径的进化起源和多样化.
- 确定 IL-17 途径在不同动物血统中的功能分歧背后的分子机制.
主要方法:
- 比较基因组学和进化分析,以追踪路径的起源.
- 在模型生物 (例如斑马鱼,昆虫) 中进行功能性测试,以研究通路相互作用和组件.
- 生物化学分析以调查域混合和蛋白质相互作用.
主要成果:
- IL-17途径起源于托尔类受体 (TLR) /IL-1R和神经类受体氨酸激酶 (RTK) 途径的融合.
- IL-17路径的进化以其祖先路径的持续交织为特征,影响了组件进化和功能多样化.
- 在无脊椎动物中,特定的神经特洛芬作为IL-17s起作用,并且与TLR/IL-1R的通路交叉通道被保留.
- 在CIKS适配器中丧失死亡域会影响NF-κB/AP-1激活和免疫力,这解释了哺乳动物的信号较弱.
结论:
- IL-17通路的独特进化历史,包括域混合和与祖先通路的持续交叉通话,推动了它的功能多样性.
- 特定域的进化损失,如CIKS中的死亡域,调节通路活动,并解释信号强度的差异.
- 这些发现为路径演变提供了洞察力,并为潜在的路径操纵提供了基础.
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