1. Hyperosmotic phase separation: Condensates beyond inclusions, granules and organelles
- Author
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Ameya P. Jalihal, Sethuramasundaram Pitchiaya, Andreas Schmidt, Saffron R. Little, Nils G. Walter, and Guoming Gao
- Subjects
0301 basic medicine ,Osmosis ,macromolecular crowding ,MLOs, membraneless organelles ,cloud formation ,Reviews ,Cytoplasmic Granules ,Biochemistry ,RNP, RNA–protein ,CPSFs, cleavage and polyadenylation factors ,Fight-or-flight response ,GEMS, genetically encoded nanoparticles ,03 medical and health sciences ,Stress granule ,Biological phase ,membraneless organelles ,biophysics ,Organelle ,UCST, upper critical saturation temperature ,Molecular Biology ,Inclusion Bodies ,Organelles ,ISR, integrated stress response ,Rna protein ,HOPS, hyperosmotic phase separation ,SGs, stress granules ,030102 biochemistry & molecular biology ,Chemistry ,Condensation ,aggregation ,protein domain ,Cell Biology ,stress response ,ALS, amyotrophic lateral sclerosis ,mesoscale organization ,LLPS, liquid–liquid phase separation ,LCST, lower critical saturation temperature ,030104 developmental biology ,Biophysics ,fluorescence ,Macromolecular crowding ,Internal organization - Abstract
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.
- Published
- 2020