bims-fascar Biomed News
on Phase separation and cellular architecture
Issue of 2020‒03‒22
two papers selected by
Victoria Yan
Max Planck Institute of Molecular Cell Biology and Genetics

  1. Anal Biochem. 2020 Mar 16. pii: S0003-2697(20)30223-2. [Epub ahead of print] 113691
    Sehgal PB, Westley J, Lerea KM, DiSenso-Browne S, Etlinger JD.
      Membraneless organelles (MLOs) in the cytoplasm and nucleus in the form of 2D and 3D phase-separated biomolecular condensates are increasingly viewed as critical in regulating diverse cellular functions. These functions include cell signaling, immune synapse function, nuclear transcription, RNA splicing and processing, mRNA storage and translation, virus replication and maturation, antiviral mechanisms, DNA sensing, synaptic transmission, protein turnover and mitosis. Components comprising MLOs often associate with low affinity; thus cell integrity can be critical to the maintenance of the full complement of respective MLO components. Phase-separated condensates are typically metastable (shape-changing) and can undergo dramatic, rapid and reversible assembly and disassembly in response to cell signaling events, cell stress, during mitosis, and after changes in cytoplasmic "crowding" (as observed with condensates of the human myxovirus resistance protein MxA). Increasing evidence suggests that neuron-specific aberrations in phase-separation properties of RNA-binding proteins (e.g. FUS and TDP43) and others (such as the microtubule-binding protein tau) contribute to the development of degenerative neurological diseases (e.g. amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer's disease). Thus, studies of liquid-like phase separation (LLPS) and the formation, structure and function of MLOs are of considerable importance in understanding basic cell biology and the pathogenesis of human diseases.
    Keywords:  2D and 3D supramolecular assemblies; Biomolecular condensates; cytoplasmic crowding; liquid-like phase separation (LLPS); membraneless organelles (MLOs); myxovirus-resistance proteins MxA and Mx1; neurodegenerative diseases
  2. Biophys Rev. 2020 Mar 18.
    Yoshizawa T, Nozawa RS, Jia TZ, Saio T, Mori E.
      Progress in development of biophysical analytic approaches has recently crossed paths with macromolecule condensates in cells. These cell condensates, typically termed liquid-like droplets, are formed by liquid-liquid phase separation (LLPS). More and more cell biologists now recognize that many of the membrane-less organelles observed in cells are formed by LLPS caused by interactions between proteins and nucleic acids. However, the detailed biophysical processes within the cell that lead to these assemblies remain largely unexplored. In this review, we evaluate recent discoveries related to biological phase separation including stress granule formation, chromatin regulation, and processes in the origin and evolution of life. We also discuss the potential issues and technical advancements required to properly study biological phase separation.
    Keywords:  Intrinsically disordered region/protein (IDR/IDP); Liquid-liquid phase separation (LLPS); Low-complexity (LC) domain; Membrane-less organelle