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细胞内pH调节低pHi的β-catenin,增加粘附和信号功能
Brandon J Czowski1, Angelina N Marchi1, Katharine A White1
1Department of Chemistry and Biochemistry, University of Notre Dame; Harper Cancer Research Institute, University of Notre Dame.
The Journal of biological chemistry
|January 9, 2026
概括
细胞内pH值 (pHi) 调节β-catenin的稳定性和功能. 低pHi稳定β-catenin,增强细胞粘附和信号,而高pHi降低其丰富性和活性.
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:
- 细胞内pH (pHi) 动力学会影响细胞中的关键过程,如增殖和迁移.
- 高的pHi通过蛋白质体降解导致β-catenin丰度下降.
- 低pHi对β-catenin的影响在很大程度上仍未被描述.
研究的目的:
- 研究低细胞内pH值 (pHi) 对β-catenin丰度,稳定性和功能的影响.
- 描述pHi作为β-catenin介导细胞过程的调节者的作用.
- 阐明pHi,β-catenin和细胞粘附和信号传递之间的关系.
主要方法:
- 用种群水平和单细胞测试来测量β-catenin水平和降解率.
- 用一个构成性稳定β-catenin突变体 (β-catenin-H36R) 来评估pH独立的稳定性.
- 在不同的pHi条件下分析附着结的组成,细胞面积和β-catenin转录活性.
主要成果:
- 低pHi稳定β-catenin,增加其在结节,细胞质和核中的丰富性.
- 在低pHi的情况下,β-catenin的半衰期会延长,在高pHi的情况下会缩短.
- 改变的pHi调节β-catenin在细胞粘附中的作用,低的pHi减少细胞面积,高的pHi增加它.
- 低pHi增强β-catenin的转录活性,模仿Wnt-on状态,而高pHi则减少它.
结论:
- 细胞内pH值充当静电控制β-catenin的丰富性,稳定性和功能.
- 对β-catenin的pH依赖调节影响细胞-细胞粘附和转录信号传递.
- 通过其粘附和信号作用,β-catenin充当了pHi依赖细胞行为的关键分子媒介.
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