通过TFEB核进出口动态,cAMP促进了急性溶解体生物发生
Saumya Bhatt1, Mohammad Ali Abbas Zaidi1, Nicholas Woods2
1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68105.
bioRxiv : the preprint server for biology
|December 15, 2025
概括
循环腺单酸盐 (cAMP) 信号通过控制转录因子EB (TFEB) 穿来调节 lysosomal 基因表达. 蛋白激酶A (PKA) 促进TFEB出口,调整 lysosomal 动态.
科学领域:
- 细胞生物学 细胞生物学
- 分子信号传输的方法
- 代谢过程中的代谢.
背景情况:
- 循环腺单酸盐 (cAMP) 信号影响脂质和葡萄糖代谢.
- lysosome-dependent降解对于细胞代谢至关重要.
- 通过cAMP信号来调节 lysosomal动力学并未得到充分理解.
研究的目的:
- 为了研究cAMP信号传递对 lysosomal动态的影响.
- 阐明转录因子EB (TFEB) 在cAMP介导的溶酶体调节中的作用.
主要方法:
- 使用福斯科林和IBMX刺激细胞内cAMP水平.
- 追踪TFEB-GFP核进出口动态.
- 对TFEB目标溶解体基因表达的分析.
- 使用H89.9抑制cAMP依赖的蛋白激酶A (PKA) 的抑制.
- 蛋白学分析,以确定酸化位点.
主要成果:
- 升高的cAMP诱导了快速的TFEB核导入和TFEB目标基因的暂时上调.
- TFEB在8小时内返回细胞质,伴随着基因下调.
- 抑制PKA导致了持续的TFEB核积累,这表明PKA促进了TFEB出口.
- 蛋白组分析显示,在TFEB出口过程中,PKA基因的酸化增加.
结论:
- 在调节 lysosomal 基因表达方面,cAMP-PKA 信号发挥着新的作用.
- TFEB核-细胞质穿是时间调节 lysosomal 活动的关键机制.
- 这种信号通路提供了关于代和 lysosomal 功能的协调的见解.
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