Liquid-liquid phase separation in biology: mechanisms, physiological functions and human diseases

细胞器 微管 细胞生物学 生物 细胞骨架 肌动蛋白 细胞质 染色质 生物发生 化学 细胞 基因 遗传学
作者
Hong Zhang,Ji Xiong,Pilong Li,Cong Liu,Jizhong Lou,Zheng Wang,Wenyu Wen,Yue Xiao,Mingjie Zhang,Xueliang Zhu
出处
期刊:Science China-life Sciences [Springer Science+Business Media]
卷期号:63 (7): 953-985 被引量:266
标识
DOI:10.1007/s11427-020-1702-x
摘要

Cells are compartmentalized by numerous membrane-enclosed organelles and membraneless compartments to ensure that a wide variety of cellular activities occur in a spatially and temporally controlled manner. The molecular mechanisms underlying the dynamics of membrane-bound organelles, such as their fusion and fission, vesicle-mediated trafficking and membrane contactmediated inter-organelle interactions, have been extensively characterized. However, the molecular details of the assembly and functions of membraneless compartments remain elusive. Mounting evidence has emerged recently that a large number of membraneless compartments, collectively called biomacromolecular condensates, are assembled via liquid-liquid phase separation (LLPS). Phase-separated condensates participate in various biological activities, including higher-order chromatin organization, gene expression, triage of misfolded or unwanted proteins for autophagic degradation, assembly of signaling clusters and actin- and microtubule-based cytoskeletal networks, asymmetric segregations of cell fate determinants and formation of pre- and post-synaptic density signaling assemblies. Biomacromolecular condensates can transition into different material states such as gel-like structures and solid aggregates. The material properties of condensates are crucial for fulfilment of their distinct functions, such as biochemical reaction centers, signaling hubs and supporting architectures. Cells have evolved multiple mechanisms to ensure that biomacromolecular condensates are assembled and disassembled in a tightly controlled manner. Aberrant phase separation and transition are causatively associated with a variety of human diseases such as neurodegenerative diseases and cancers. This review summarizes recent major progress in elucidating the roles of LLPS in various biological pathways and diseases.
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