控制ENaC无处不在的控制
Shujie Shi1, Gustavo Frindt2, Sarah Christine M Whelan1
1Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.
American journal of physiology. Renal physiology
|June 13, 2024
概括
皮质通道 (ENaC) γ亚单元的无处不在是由其细胞位置决定的,而不是它的分裂状态. 细胞内水平的增加也可以刺激ENaC的泛化,影响道表达.
科学领域:
- 细胞生物学 细胞生物学
- 分子生理学分子生理学
- 膜蛋白调节法 膜蛋白调节法
背景情况:
- 乌比基因化是一种关键的翻译后修饰,它调节了蛋白质的稳定性和流通.
- 皮质通道 (ENaC) 在平衡中起着至关重要的作用.
- 此前已经报告了ENaC γ子单元的成熟,分裂形式的选择性泛化.
研究的目的:
- 阐明控制ENaC γ子单元的选择性无所不在的机制.
- 为了确定蛋白质分裂或细胞位置是否决定了γENaC无处不在.
- 为了研究细胞内水平对ENaC无化的影响.
主要方法:
- 使用了原生动物脏和异质表达的费舍尔鼠甲状腺 (FRT) 细胞.
- 研究的野生类型和分裂部位废除了与α-和βENaC共同表达的γENaC突变体.
- 用于现场表面生物化和克拉特林介导的内细胞酶抑制 (Dyngo-4a).
- 在不同的细胞内条件下 (阿米洛里德,单宁素,Na+补充) 评估了无处不在的水平.
主要成果:
- 单独分裂和完全分裂的γENaC都具有强烈的泛化,这表明分裂不必.
- 当分裂部位废除的突变物与其他ENaC子单元共同表达时,发生了ubiquitination,从而促进了Golgi贩运.
- 在顶端和下顶端的两个部分都发生了化,这表明靠近顶端膜的位置很重要.
- 抑制内细胞化增加了细胞表面和无处不在的gENaC.
- 细胞内的增加 (通过单宁素或Na+补充) 增强了γENaC的无化,并降低了ENaC的表达.
结论:
- γENaC的无处不在特异性主要取决于它的细胞位置,特别是在或靠近顶膜,而不是它的分裂状态.
- 细胞内度的增加可以刺激γENaC的泛化,导致整体ENaC表达的减少.
- 这些发现提供了对ENaC活动和表达通过无处不在依赖路径的调节的见解.
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