Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway | |
Wang,Zheng1; Chen,Di1,2; Guan DS(关东石)3; Liang,Xiaobo2,4; Xue,Jianfeng5; Zhao HY(赵宏宇)1; Song,Guangtao2,4; Lou,Jizhong2,4; He,Yan5; Zhang,Hong1,2 | |
刊名 | JOURNAL OF CELL BIOLOGY |
2022-03-16 | |
卷号 | 221期号:5页码:27 |
ISSN号 | 0021-9525 |
DOI | 10.1083/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. |
分类号 | 二类/Q1 |
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关键词 | PROTEIN ; DROPLETS ; PHOSPHORYLATION ; DETERMINES ; MATURATION ; GRANULES ; DYNAMICS ; SYSTEM ; CELLS |
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 |
其他责任者 | Zhang, Hong |
内容类型 | 期刊论文 |
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 |
作者单位 | 1.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China; 2.Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China; 3.Chinese Acad Sci, Inst Mech, State Key Lab Nonlinear Mech, Beijing, Peoples R China; 4.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Key Lab RNA Biol, Beijing, Peoples R China; 5.Tsinghua Univ, Dept Chem, Key Lab Bioorgan Phosphorus Chem & Chem Biol, Minist Educ, Beijing, Peoples R China |
推荐引用方式 GB/T 7714 | Wang,Zheng,Chen,Di,Guan DS,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.,关东石.,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. |
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