不激活皮质分支活性蛋白的负调节剂可增强单细胞迁移的持久性
Artem I Fokin1, Arthur Boutillon2, John James1
1CNRS UMR7654, Ecole Polytechnique, Institut Polytechnique de Paris, 91120 Palaiseau, France.
Journal of cell science
|December 7, 2023
概括
禁用抑制分支性actin聚合的三种蛋白质,大大增加了细胞迁移. 这个这个这个这个这个
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 该Rac1-WAVE-Arp2/3通路通过在血膜上聚合分支性乙烯来驱动细胞迁移.
- 像arpin,ARPC1A和CYFIP2这样的负调节剂控制了分支性actin聚合.
- 了解这些调节剂是控制细胞运动的关键.
研究的目的:
- 为了研究使三种负调节器的分支性行为因子聚合:arpin,ARPC1A和CYFIP2.2无活化的综合效应.
- 确定对细胞迁移持久性和集体细胞行为的影响.
- 探索维门丁在观察到的"超级迁徙者"表型中的作用.
主要方法:
- 使用KD和KO策略,在人类乳腺MCF10A细胞和斑马鱼内皮细胞中禁用arpin,ARPC1A和CYFIP2.
- 评估细胞迁移在单细胞中的持久性和集体行为,如伤口愈合和acinus形态发生.
- 分析了维敏 (VIM) 表达水平,并通过重新表达维敏进行了救援实验.
主要成果:
- 与单次或双次不激活相比,三次不激活arpin,ARPC1A和CYFIP2显著增强了细胞迁移持久性.
- 三重KO细胞中的"超级迁移"表型与异质的维门丁下调和受损的集体细胞行为有关.
- 在三重KO细胞中重新表达维门丁,部分恢复了单细胞迁移的正常持久性.
结论:
- 同时抑制多个负调节器的分支性actin聚合,强烈促进细胞迁移.
- 维门丁下调似乎是维持三重KO细胞中观察到的增强迁移状态的关键因素.
- 细胞皮层持续过度分支的活性蛋白生产可以通过基因表达变化诱导持久的运动状态.
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