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 molecu...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.展开更多
基金supported by grants from the Beijing Municipal Science and Technology Committee (Z181100001318003)the National Natural Science Foundation of China (31421002, 31561143001,31630048, and 31790403)+17 种基金the National Natural Science Foundation of China (91853113 and 31872716)the National Natural Science Foundation of China (11672317)the National Natural Science Foundation of China (31871394 and 31670730)supported by grants from the National Natural Science Foundation of China (31420103916 and 31991192)the Ministry of Science and Technology of China (2017YFA0503401)supported by grants from the Ministry of Science and Technology of China (2019YFA0707000)supported by grants from the Ministry of Science and Technology of China (2019YFA0508401)the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB19000000)the Key Research Program of Frontier Sciences, CAS (QYZDY-SSW-SMC006)supported by funds from the Ministry of Science and Technology of China and the National Natural Science Foundation of China (2017YFA0506600 and 31871309)supported by funds from the Ministry of Science and Technology of China and the National Natural Science Foundation of China (2019YFA0508403 and 31871443)supported by grants from the Ministry of Science and Technology of China (2016YFA0501902)the Science and Technology Commission of Shanghai Municipality (18JC1420500)the Shanghai Municipal Science and Technology Major Project (2019SHZDZX02)the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01)CAS (XDB19020102)supported by grants from RGC of Hong Kong (AoE-M09-12 and C6004-17G)National Key R&D Program of China (2016YFA0501903 and 2019YFA0508402)。
文摘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.
