构成性安德罗斯坦受体和过氧体增殖器激活受体α 在细胞中不进行液态-液态相分离
Pengfei Zhao1, Shicheng Fan1, Yanying Zhou1
1NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong Provincial Key Laboratory of New Drug Screening and Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China (P.Z., S.F., H.B.); Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (P.Z., S.F., Y.Z., M.H., Y.G., H.B.); and The State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, 518055, China (H.B.).
构成性安德罗斯坦受体 (CAR) 和过氧体增殖器激活受体α (PPARα) 不经历相分离. 激活或压力不会诱导细胞中CAR和PPARα凝结物的形成.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 分子内分泌学分子内分泌学
背景情况:
- 核受体如构成性安德罗斯坦受体 (CAR) 和过氧体增殖器激活受体α (PPARα) 调节关键的生理过程.
- 阶段分离,形成类似液体的凝聚物,对于细胞功能至关重要,包括转录调节.
- CAR和PPARα的相分离行为仍然未被探索.
研究的目的:
- 调查CAR和PPARα相分离的可能性.
- 为了确定细胞应激或受体激活是否影响CAR和PPARα相分离.
主要方法:
- 在CAR和PPARα中对本质上混乱的区域进行计算分析.
- 实验性测定包括高体应激和激动剂治疗.
- 使用蓝光刺激来评估凝结物形成的OptoDroplets测定.
主要成果:
- 计算分析表明,CAR和PPARα经历相位分离的可能性很低.
- 实验分析证实,在各种条件下,CAR和PPARα没有相分离.
- 在OptoDroplets测定中,没有发现与CAR或PPARα融合蛋白形成凝结物.
结论:
- 无论是CAR还是PPARα,在激活时或在高位应激下都不会表现出相位分离.
- 这些发现澄清了CAR和PPARα在细胞环境中的生物物理行为.
- 提供了对控制CAR和PPARα功能的分子机制的新见解.
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