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Liquid-liquid phase separation as a common organizing principle of intracellular space and biomembranes providing dynamic adaptive responses
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2021-07-20 , DOI: 10.1016/j.bbamcr.2021.119102
Semen V Nesterov 1 , Nikolay S Ilyinsky 2 , Vladimir N Uversky 3
Affiliation  

This work is devoted to the phenomenon of liquid-liquid phase separation (LLPS), which has come to be recognized as fundamental organizing principle of living cells. We distinguish separation processes with different dimensions. Well-known 3D-condensation occurs in aqueous solution and leads to membraneless organelle (MLOs) formation. 2D-films may be formed near membrane surfaces and lateral phase separation (membrane rafts) occurs within the membranes themselves. LLPS may also occur on 1D structures like DNA and the cyto- and nucleoskeleton. Phase separation provides efficient transport and sorting of proteins and metabolites, accelerates the assembly of metabolic and signaling complexes, and mediates stress responses. In this work, we propose a model in which the processes of polymerization (1D structures), phase separation in membranes (2D structures), and LLPS in the volume (3D structures) influence each other. Disordered proteins and whole condensates may provide membrane raft separation or polymerization of specific proteins. On the other hand, 1D and 2D structures with special composition or embedded IDRs can nucleate condensates. We hypothesized that environmental change may trigger a LLPS which can propagate within the cell interior moving along the cytoskeleton or as an autowave. New phase propagation quickly and using a low amount of energy adjusts cell signaling and metabolic systems to new demands. Cumulatively, the interconnected phase separation phenomena in different dimensions represent a previously unexplored system of intracellular communication and regulation which cannot be ignored when considering both physiological and pathological cell processes.



中文翻译:

液-液相分离作为细胞内空间和生物膜的常见组织原理,提供动态适应性响应

这项工作致力于研究液-液相分离 (LLPS) 现象,该现象已被公认为是活细胞的基本组织原理。我们区分不同维度的分离过程。众所周知的 3D 缩合发生在水溶液中并导致无膜细胞器 (MLO) 的形成。2D 薄膜可能在膜表面附近形成,并且在膜本身内发生横向相分离(膜筏)。LLPS 也可能发生在一维结构上,如 DNA 和细胞骨架和核骨架。相分离提供蛋白质和代谢物的有效运输和分类,加速代谢和信号复合物的组装,并介导压力反应。在这项工作中,我们提出了一个模型,其中聚合过程(一维结构),膜中的相分离(2D 结构)和体积中的 LLPS(3D 结构)相互影响。无序的蛋白质和完整的凝聚物可以提供膜筏分离或特定蛋白质的聚合。另一方面,具有特殊成分或嵌入 IDR 的一维和二维结构可以使凝聚物成核。我们假设环境变化可能会触发 LLPS,它可以在细胞内部沿细胞骨架移动或作为自波传播。新阶段的快速传播和使用少量能量可根据新需求调整细胞信号和代谢系统。累计,

更新日期:2021-07-26
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