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Hyperosmotic phase separation: Condensates beyond inclusions granules and organelles

机译:Hypermotmist分离:除夹杂物颗粒和细胞器之外的缩合

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摘要

Biological liquid–liquid phase separation has gained considerable attention in recent years as a driving force for the assembly of subcellular compartments termed membraneless organelles. The field has made great strides in elucidating the molecular basis of biomolecular phase separation in various disease, stress response, and developmental contexts. Many important biological consequences of such “condensation” are now emerging from in vivo studies. Here we review recent work from our group and others showing that many proteins undergo rapid, reversible condensation in the cellular response to ubiquitous environmental fluctuations such as osmotic changes. We discuss molecular crowding as an important driver of condensation in these responses and suggest that a significant fraction of the proteome is poised to undergo phase separation under physiological conditions. In addition, we review methods currently emerging to visualize, quantify, and modulate the dynamics of intracellular condensates in live cells. Finally, we propose a metaphor for rapid phase separation based on cloud formation, reasoning that our familiar experiences with the readily reversible condensation of water droplets help understand the principle of phase separation. Overall, we provide an account of how biological phase separation supports the highly intertwined relationship between the composition and dynamic internal organization of cells, thus facilitating extremely rapid reorganization in response to internal and external fluctuations.
机译:近年来,生物液 - 液相分离的关注是亚细胞室组装被称为膜无细胞器的驱动力。该领域在阐明了各种疾病,应激反应和发育背景下阐明了生物分子间分离的分子基础。这种“凝结”的许多重要生物后果现在在体内研究中出现。在这里,我们审查了我们组的最近的工作以及其他表现出许多蛋白质在蜂窝反应中经历的快速,可逆凝结,对渗透性变化的无处不在的环境波动。我们将分子拥挤作为这些反应中的缩合的重要驾驶员,并表明蛋白质组的显着分数是在生理条件下进行相分离。此外,我们审查目前出现的方法以可视化,量化和调节活细胞中细胞内缩合物的动态。最后,我们提出了一种基于云层的快速相位分离的隐喻,推理我们熟悉的水滴易于可逆凝结的经验有助于了解相分离的原理。总的来说,我们提供了生物相分离如何支持组成和动态内部组织之间高度交织的关系的说明,从而促进了响应内部和外部波动的极快重新组织。

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