mTOR通过ULK1-依赖和ULK1-独立的机制调节矿物质皮质体受体的转录活性
Yusuf Ali1,2, Celso E Gomez-Sanchez1,2, Maria Plonczynski2
1Research Service, G. V. (Sonny) Montgomery VA Medical Center, Jackson, MS 39216, USA.
Endocrinology
|February 7, 2024
概括
拉巴胺素的机械标 (mTOR) 通过防止其被Unc-51-like激酶 (ULK1) 失活,并通过直接关联,影响基因转录和细胞功能来调节矿物质皮质类受体 (MR).
科学领域:
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
- 内分泌学 在内分泌学.
背景情况:
- 矿物质皮质体受体 (MR) 是一个关键的转录因子,调节基因表达,用于诸如电解质平衡等重要功能.
- 之前的研究表明,Unc-51-like激酶 (ULK1) 化并抑制MR,而拉巴胺素 (mTOR) 的机械点禁用ULK1,从而防止MR的失活.
研究的目的:
- 研究ULK1和mTOR在MR活动和转录中的调控作用.
- 阐明mTOR影响MR功能的机制,包括潜在的直接相互作用.
主要方法:
- 使用了M1小鼠皮质收集管细胞,表达大鼠MR和记者基因.
- 使用ULK1和mTOR的药理抑制剂,以及CRISPR/gRNA用于猛龙和瑞克托的敲击.
- 通过共同沉评估了MR交换活化,记者基因活性,内源基因转录和蛋白质相互作用.
主要成果:
- ULK1抑制增强了联体诱导的MR转换活化;ULK1活化没有影响.
- mTOR抑制和淘汰猛禽/猛减少酸化ULK1,MR激活和目标基因转录.
- 在血清843 (MR-S843A) 中突变MR阻断了ULK1的作用,但仅部分抑制了mTOR对转录的影响.
- 发现mTOR,Raptor和Rictor与MR共同沉,而多会增加它们的酸化状态.
结论:
- mTOR通过两种途径显著调节MR活性:抑制ULK1介导的无活化和直接关联机制.
- 这些发现为ULK1和mTOR在细胞能量状态监测和MR调节中的作用提供了新的见解.
关键词:
在M1细胞中,M1细胞是M1细胞.猛禽猛禽是一种猛禽.里克托尔·里克托尔 (Rictor Rictor) 是一个著名的艺术家.ULK1 是一个ULK1阿尔多斯氨酸是一种阿尔多斯氨酸.在mTOROR中使用mTOR.矿物质皮质类受体受体更多相关视频
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