通过转录因子NFAT5直接感知和减轻离子应力
Chandni B Khandwala1, Parijat Sarkar1, H Broder Schmidt1
1Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science advances
|February 19, 2025
概括
动物细胞具有一种新的机制,可以使用NFAT5蛋白检测和管理离子应激. 这种蛋白质的蛋白质.
科学领域:
- 细胞生物学 细胞生物学
- 分子机制的分子机制
- 环境应激反应环境应激反应
背景情况:
- 气候变化引起的气温上升和水资源短缺会提高细胞的离子强度,导致离子应激.
- 离子压力会破坏细胞的基本功能,包括蛋白质,有机体和基因组完整性.
- 现有的知识缺乏对动物细胞如何感知和减轻细胞内离子应激的清晰理解.
研究的目的:
- 确定和描述动物细胞感知和响应细胞内离子强度的分子机制.
- 阐明NFAT5蛋白在调解细胞适应离子应激中的作用.
- 为了比较动物细胞对离子压力的反应,与其他生物体 (如酵母) 中已知的机制进行比较.
主要方法:
- 研究了转录因子NFAT5及其C端类域 (PLD) 在感知离子强度方面的功能.
- 采用了体外测试来观察在不同离子强度下纯化NFAT5PLD形成的冷凝物.
- 采用酵母模型来评估人类NFAT5在重建对离子应激的转录反应中的充分性.
主要成果:
- 确定NFAT5作为细胞内离子强度的直接传感器,利用其C端类域 (PLD).
- 证明NFAT5 PLD对于通过BRD4招募协调适应性基因表达程序至关重要且足够.
- 展示了纯化的NFAT5 PLD在高离子强度和人类NFAT5在体外形成凝结物的能力,以拯救酵母离子应激反应.
结论:
- 在动物细胞中,NFAT5充当细胞内离子强度的单蛋白传感器.
- NFAT5 PLD通过对离子敏感的形状变化直接调节转录,以保持离子平衡.
- 这种机制代表了与酵母高度甘油醇途径相比,用于减轻离子应激的独特途径.
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