通过两种不同的机制,NHSL3控制单细胞和集体细胞迁移
Nikita M Novikov1, Jinmei Gao2, Artem I Fokin1
1Laboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de Paris, Palaiseau, France.
Nature communications
|January 2, 2025
概括
类似于Nance-Horan综合征3 (NHSL3) 蛋白质异型明显调节细胞迁移. 特定的相互作用控制单细胞运动和集体细胞迁移动态,揭示了新的分子机制.
科学领域:
- 细胞生物学 细胞生物学
- 分子机制的分子机制
- 遗传学 遗传学 是一个
背景情况:
- 细胞迁移的分子基础尚未完全阐明.
- 类似于Nance-Horan综合征3 (NHSL3) 是最近发现的基因家族成员.
研究的目的:
- 研究NHSL3在单细胞和集体细胞迁移中的作用.
- 为了识别特定的NHSL3异型及其蛋白质相互作用对于不同的迁移行为至关重要.
主要方法:
- 利用淘汰细胞模型来评估迁移持久性和追随细胞行为.
- 采用蛋白质组学来确定NHSL3异型的合作伙伴谱.
- 应用基于AlphaFold2的管道来预测蛋白质-蛋白质相互作用和结合部位.
- 与特定的NHSL3异型和突变的结合位进行了救援实验.
主要成果:
- 在NHSL3淘汰细胞中,单细胞迁移的持久性增加,但在集体迁移中,追随细胞功能受损.
- 独特的NHSL3异构体与不同的蛋白质合作伙伴相互作用:长异构体与MENA/VASP在细胞结处相互作用,短异构体与14-3-3θ在lamellipodia相互作用.
- 关键结合点的突变取消了救援效应,证实了这些相互作用的功能重要性.
结论:
- 在Lamellipodia中,NHSL3通过与14-3-3θ的相互作用来调节单细胞迁移.
- NHSL3通过与MENA/VASP蛋白在细胞结点的相互作用来调节集体细胞迁移.
- NHSL3采用不同的分子机制来控制不同模式的细胞迁移.
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