托尔类受体9的ectodomain被切割,以产生一个功能性受体
Sarah E Ewald1, Bettina L Lee, Laura Lau
1Division of Immunology & Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, 405 Life Sciences Addition, Berkeley, California 94720-3200, USA.
Nature
|September 30, 2008
概括
收费类受体 (TLRs) 7和9在内分泌体中被处理,其中ectodomain裂变激活了它们的免疫功能. 这种裂变阻止了自我核酸的识别,避免了自身免疫.
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:
- 哺乳动物托尔类受体 (TLRs) 3,7,8和9识别微生物核酸以启动免疫反应.
- 通过TLRs对自身核酸的失调识别可以导致自身免疫.
- 控制TLR7和TLR9功能的精确细胞传输和定位机制尚不清楚.
研究的目的:
- 阐明TLR9和TLR7从内质网膜到内酶体的细胞内运输途径.
- 为了研究TLR9和TLR7外域分裂在内分泌体内的处理和功能后果.
主要方法:
- 利用小鼠巨细胞和树突细胞来追踪TLR9和TLR7的贩运.
- 分析了在内解体体区内受体外皮层裂变的分析.
- 评估了全长TLR9形式的联结和MyD88招募能力. 与切割的TLR9形式相比.
主要成果:
- 定义了TLR9和TLR7传输到免疫细胞内内酶体的途径.
- 证明了TLR9和TLR7外分主体在内溶酶体内被蛋白质分解分离.
- 确定了TLR9的切割形式,而不是全长的,作为招募MyD88.8.的功能受体.
- 表明防止裂变或强迫表面定位使TLR9变得无功能.
结论:
- 对于TLR9和TLR7在内分泌体中的功能来说,它们的内分泌体分裂是必不可少的.
- 这种裂变机制限制了受体激活到内解酶体区.
- 裂变作为一种关键的监管策略,以防止TLR介导的对自身核酸的反应,并保持免疫耐受性.
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