通过保持gp96的稳定性,ER居民CCDC134保护TLR4的成熟
Yang Bai1, Chao Zhang1,2, Hao Liu1
1State Key Laboratory of Immune Response and Immunotherapy, State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China.
概括
CCDC134蛋白对于内质网膜中托尔类受体4 (TLR4) 的成熟至关重要. 它通过控制糖蛋白96 (gp96) 糖化,防止TLR4降解来调节TLR4的炎症反应.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 收费类受体4 (TLR4) 在感知危险信号时启动炎症反应.
- TLR4的成熟过程包括在内质网膜 (ER) 中进行合成,糖化和运输到等离子体膜.
- 在ER中TLR4加工和成熟的机制尚未完全理解.
研究的目的:
- 确定涉及托尔类受体4 (TLR4) 成熟和炎症信号传递的关键因素.
- 阐明CCDC134在TLR4.4的内细胞网膜 (ER) 处理中的作用.
主要方法:
- 采用全基因组的CRISPR查来确定TLR4信号传递的重要因素.
- 细胞局部化研究评估了CCDC134在ER光线与分泌中的作用.
- 在CCDC134贫乏细胞中分析TLR4的贩运,降解和其伴侣糖蛋白96 (gp96) 的糖化.
主要成果:
- 鉴定出CCDC134是TLR4依赖性炎症反应的关键因素.
- CCDC134的功能需要它在ER光线内定位.
- 由于异常的gp96糖化和不稳定,CCD134的损失导致ER保留和TLR4的降解.
- CCDC134对于适当的TLR4成熟和等离子体膜传输至关重要.
结论:
- CCDC134控制了ER中的糖蛋白96 (gp96) 糖化.
- 这种由CCDC134进行的调控有助于托尔类受体4 (TLR4) 的成熟和贩运.
- CCDC134是TLR4处理和随后的炎症免疫反应的关键调节者.
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