化基因受体异质寡合体调节单细胞的化学作用
Garrett A Enten1,2, Xianlong Gao1, Michelle Y McGee1
1Department of Surgery, University of South Florida, Morsani College of Medicine, Tampa, FL, USA.
Life science alliance
|May 23, 2024
概括
压力激素通过形成受体复合体来调节免疫细胞的运动. 氨酸血管压素受体1A (AVPR1A) 和上腺素受体 (ARs) 与化学激素受体 (CRs) 相互作用,在压力期间控制免疫细胞的贩运.
科学领域:
- 分子药理学分子药理学
- 免疫学 免疫学 免疫学
- 细胞信号传输 细胞信号传输
背景情况:
- 压力显著影响免疫细胞功能,但分子机制在很大程度上仍未知.
- 已知化学受体 (CRs) 与α1-上腺受体 (α1-ARs) 异构,从而影响CR调节.
- 氨酸血管压素受体1A (AVPR1A) 参与各种生理过程,包括应激反应.
研究的目的:
- 研究氨酸压素受体1A (AVPR1A) 与各种人体化学因子受体 (CRs) 的异构化.
- 阐明AVPR1A:CR异构体在调节免疫细胞化学反应中的作用.
- 确定压力激素如何通过AVPR1A和α1-ARs调节通过这些受体复合体的免疫细胞贩运.
主要方法:
- 重组表达系统研究AVPR1A和CR异构化.
- 在THP-1细胞和初级人类单细胞中检测异构体.
- 生物发光共振能量转移 (BRET) 用于监测G蛋白激活.
- 编辑CRISPR/Cas9基因以创建缺乏AVPR1A或α1B-AR的THP-1细胞.
主要成果:
- 在体外和免疫细胞中,AVPR1A与大多数人体CRs (CXCR1除外) 形成异构体.
- 无干的AVPR1A差异调节了CR介导化学反应的疗效.
- AVPR1A干破坏AVPR1A:CR异构体,改变化疗作用 (增强CCR1,抑制CCR2,CCR8,CXCR4).
- 相互依赖的CRs,α1B/D-ARs和AVPR1A的异质寡合体复合体控制CR介导的化学反应.
结论:
- 通过与CRs的异构化,AVPR1A在调节免疫细胞化学反应方面发挥着重要作用.
- 压力激素可以通过准这些复杂的异质寡合体受体结构来调节免疫细胞的贩运.
- 这些发现揭示了一种新的分子机制,它将压力,受体复合体和免疫细胞功能联系起来.
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