基于Nox1的NADPH氧化酶调节了Par蛋白复合物的活性,以控制细胞极化
Alejandra Valdivia1, Charity Duran1, Mingyoung Lee1
1Division of Cardiology, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, United States.
Frontiers in cell and developmental biology
|August 28, 2023
概括
缺少Nox1会通过破坏Par3/aPKC复合体和失活PP2A酸酶,损害细胞极性和拉美利波的形成. 过氧化 (H2O2) 的添加挽救了这些缺陷,突出了Nox1 .
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细胞迁移对于生物和病理过程至关重要,需要精确的前后极性和状形形成.
- 分割缺陷 (Par) 蛋白质复合体 (Par3,Par6,aPKC) 和小GTPases (Rac,Cdc42,RhoA) 是细胞极性和迁移的关键调节者.
- 基于NOx1的NADPH氧化酶与生长因子诱导的细胞迁移有关.
研究的目的:
- 研究Nox1在确定细胞极性和调节细胞迁移期间Par复合物的作用.
- 阐明Nox1缺陷影响细胞极性和乳脂形成的分子机制.
- 在新极端增生症的小鼠模型中评估Nox1-PP2A-aPKC信号轴的生理相关性.
主要方法:
- 分析细胞极性,MTOC定位和Nox1缺乏细胞中的拉美利波底形成.
- 调查Par3,Tiam,Rac1,aPKC和PP2A酸酶活性,以应对Nox1缺乏和H2O2治疗.
- 在Nox1缺乏的小鼠主性大动脉光滑肌细胞 (MASMCs) 和大腿动脉线损伤模型中进行验证.
主要成果:
- 缺乏Nox1的细胞表现出缺陷的前后极性,MTOC极化和单片形形成,而不是形成多个突起.
- 诺克斯1缺乏导致PP2A酸酶失活,随后aPKC激活,导致Par3,Tiam和Rac1的过度激活.
- 外源H2O2拯救了Nox1-缺乏细胞中的迁移缺陷;Nox1-/-小鼠显示减少了与PP2A和aPKC活动相关的新极端增生症.
结论:
- 诺克斯1对于确定细胞极性和正确的拉美利波底形成至关重要,可能通过调节PP2A酸酶和aPKC活性.
- Nox1-PP2A-aPKC信号通路在控制细胞迁移方面发挥着关键作用,并对血管重塑有影响.
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