3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Hyperosmotic phase separation: Condensates beyond inclusions, granules and organelles

      review-article

      1 , 2 , 1 , 1 , 3 , 1 , 4 , 5 , 6 , 1 ,

      The Journal of Biological Chemistry

      American Society for Biochemistry and Molecular Biology

      macromolecular crowding, stress response, protein domain, aggregation, biophysics, fluorescence, membraneless organelles, cloud formation, mesoscale organization, ALS, amyotrophic lateral sclerosis, CPSFs, cleavage and polyadenylation factors, GEMS, genetically encoded nanoparticles, HOPS, hyperosmotic phase separation, ISR, integrated stress response, LCST, lower critical saturation temperature, LLPS, liquid–liquid phase separation, MLOs, membraneless organelles, RNP, RNA–protein, SGs, stress granules, UCST, upper critical saturation temperature

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references 137

          • Record: found
          • Abstract: found
          • Article: not found

          The integrated stress response.

          In response to diverse stress stimuli, eukaryotic cells activate a common adaptive pathway, termed the integrated stress response (ISR), to restore cellular homeostasis. The core event in this pathway is the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) by one of four members of the eIF2α kinase family, which leads to a decrease in global protein synthesis and the induction of selected genes, including the transcription factor ATF4, that together promote cellular recovery. The gene expression program activated by the ISR optimizes the cellular response to stress and is dependent on the cellular context, as well as on the nature and intensity of the stress stimuli. Although the ISR is primarily a pro-survival, homeostatic program, exposure to severe stress can drive signaling toward cell death. Here, we review current understanding of the ISR signaling and how it regulates cell fate under diverse types of stress.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Biomolecular condensates: organizers of cellular biochemistry

            In addition to membrane-bound organelles, eukaryotic cells feature various membraneless compartments, including the centrosome, the nucleolus and various granules. Many of these compartments form through liquid–liquid phase separation, and the principles, mechanisms and regulation of their assembly as well as their cellular functions are now beginning to emerge.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Liquid phase condensation in cell physiology and disease.

              Phase transitions are ubiquitous in nonliving matter, and recent discoveries have shown that they also play a key role within living cells. Intracellular liquid-liquid phase separation is thought to drive the formation of condensed liquid-like droplets of protein, RNA, and other biomolecules, which form in the absence of a delimiting membrane. Recent studies have elucidated many aspects of the molecular interactions underlying the formation of these remarkable and ubiquitous droplets and the way in which such interactions dictate their material properties, composition, and phase behavior. Here, we review these exciting developments and highlight key remaining challenges, particularly the ability of liquid condensates to both facilitate and respond to biological function and how their metastability may underlie devastating protein aggregation diseases.
                Bookmark

                Author and article information

                Contributors
                Journal
                J Biol Chem
                J Biol Chem
                The Journal of Biological Chemistry
                American Society for Biochemistry and Molecular Biology
                0021-9258
                1083-351X
                23 November 2020
                2021
                23 November 2020
                : 296
                Affiliations
                [1 ]Single Molecule Analysis Group and Center for RNA Biomedicine, Department of Chemistry, University of Michigan, Ann Arbor, Michigan, USA
                [2 ]Cell and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, Michigan, USA
                [3 ]Biophysics Graduate Program, University of Michigan, Ann Arbor, Michigan, USA
                [4 ]Program in Chemical Biology, University of Michigan, Ann Arbor, Michigan, USA
                [5 ]Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
                [6 ]Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
                Author notes
                []For correspondence: Nils G. Walter nwalter@ 123456umich.edu
                Article
                S0021-9258(20)00030-7 100044
                10.1074/jbc.REV120.010899
                7948973
                33168632
                © 2020 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                Categories
                Reviews

                Comments

                Comment on this article