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Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway

文献类型：期刊论文

作者Wang, Zheng5; Chen, Di4,5; Guan, Dongshi3; Liang, Xiaobo2,4; Xue, Jianfeng1; Zhao, Hongyu5; Song, Guangtao2,4; Lou, Jizhong2,4; He, Yan1; Zhang, Hong4,5
刊名JOURNAL OF CELL BIOLOGY
出版日期2022-03-16
卷号221期号:5页码:27
ISSN号0021-9525
DOI10.1083/jcb.202112024
通讯作者Zhang, Hong(hongzhang@ibp.ac.cn)
英文摘要Very little is known about how the material properties of protein condensates assembled via liquid-liquid phase separation (LLPS) are maintained and affect physiological functions. Here we show that liquid-like condensates of the transcription factor TFEB exhibit low fusion propensity in vitro and in living cells. We directly measured the attraction force between droplets, and we characterized the interfacial tension, viscosity, and elasticity of TFEB condensates. TFEB condensates contain rigid interfacial boundaries that govern their interaction behaviors. Several small molecules, including Ro-3306, modify the material properties of TFEB condensates, increasing their size and fusion propensity. These compounds promote lysosomal biogenesis and function in a TFEB-dependent manner without changing its cytoplasmic-nuclear translocation. Ro-3306 promotes autophagy activity, facilitating degradation of toxic protein aggregates. Our study helps explain how protein condensates are maintained as physically separate entities and reveals that the material properties of TFEB condensates can be harnessed to modulate TFEB activity.
WOS关键词PROTEIN ; DROPLETS ; PHOSPHORYLATION ; DETERMINES ; MATURATION ; GRANULES ; DYNAMICS ; SYSTEM ; CELLS
资助项目Chinese Ministry of Science and Technology[2017YFA0503401] ; Beijing Municipal Science and Technology Committee[Z181100001318003] ; National Natural Science Foundation of China[92054301] ; National Natural Science Foundation of China[31790403] ; National Natural Science Foundation of China[31871426] ; Key Research Program of Frontier Sciences from the Chinese Academy of Sciences[QYZDYSSW-SMC006]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000867730300001
资助机构Chinese Ministry of Science and Technology ; Beijing Municipal Science and Technology Committee ; National Natural Science Foundation of China ; Key Research Program of Frontier Sciences from the Chinese Academy of Sciences
源URL[http://dspace.imech.ac.cn/handle/311007/90400]  
专题力学研究所_非线性力学国家重点实验室
通讯作者Zhang, Hong
作者单位1.Tsinghua Univ, Dept Chem, Key Lab Bioorgan Phosphorus Chem & Chem Biol, Minist Educ, Beijing, Peoples R China
2.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Key Lab RNA Biol, Beijing, Peoples R China
3.Chinese Acad Sci, Inst Mech, State Key Lab Nonlinear Mech, Beijing, Peoples R China
4.Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China
5.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Zheng,Chen, Di,Guan, Dongshi,et al. Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway[J]. JOURNAL OF CELL BIOLOGY,2022,221(5):27.
APA Wang, Zheng.,Chen, Di.,Guan, Dongshi.,Liang, Xiaobo.,Xue, Jianfeng.,...&Zhang, Hong.(2022).Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway.JOURNAL OF CELL BIOLOGY,221(5),27.
MLA Wang, Zheng,et al."Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway".JOURNAL OF CELL BIOLOGY 221.5(2022):27.

入库方式： OAI收割

来源：力学研究所

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