National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
Sci China Life Sci. 2020 Jul;63(7):953-985. doi: 10.1007/s11427-020-1702-x. Epub 2020 Apr 30.
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.
细胞通过多种膜包裹的细胞器和无膜隔间进行分隔，以确保各种细胞活动以时空受控的方式进行。膜结合细胞器的动力学的分子机制，如融合和裂变、囊泡介导的运输以及膜接触介导的细胞器间相互作用，已经得到了广泛的描述。然而，无膜隔间的组装和功能的分子细节仍然难以捉摸。最近有大量证据表明，大量无膜隔间，统称为生物大分子凝聚物，是通过液-液相分离（LLPS）组装的。相分离凝聚物参与各种生物活动，包括高级染色质组织、基因表达、错误折叠或不需要的蛋白质的分拣进行自噬降解、信号簇的组装以及肌动蛋白和微管为基础的细胞骨架网络、细胞命运决定因素的不对称分离以及前突触和后突触密度信号组装的形成。生物大分子凝聚物可以转变为不同的物质状态，如凝胶状结构和固体聚集体。凝聚物的物质特性对于实现其独特的功能至关重要，如生化反应中心、信号枢纽和支撑结构。细胞已经进化出多种机制来确保生物大分子凝聚物以严格控制的方式进行组装和拆卸。异常的相分离和转变与多种人类疾病如神经退行性疾病和癌症有关。本综述总结了阐明 LLPS 在各种生物途径和疾病中的作用的最新重大进展。
