bims-fascar Biomed News
on Phase separation and cellular architecture
Issue of 2019–06–09
two papers selected by
Victoria Tianjing Yan, Max Planck Institute of Molecular Cell Biology and Genetics
  1. Arp2/3 complex-driven spatial patterning of the BCR enhances immune synapse formation, BCR signaling and cell activation.
  2. Intrinsic Disorder-Based Emergence in Cellular Biology: Physiological and Pathological Liquid-Liquid Phase Transitions in Cells.
  1. Elife. 2019 Jun 03. pii: e44574. [Epub ahead of print]8
    Arp2/3 complex-driven spatial patterning of the BCR enhances immune synapse formation, BCR signaling and cell activation.
    Madison Bolger-Munro, Kate Choi, Joshua M Scurll, Libin Abraham, Rhys S Chappell, Duke Sheen, May Dang-Lawson, Xufeng Wu, John J Priatel, Daniel Coombs, John A Hammer, Michael R Gold.
      When B cells encounter antigens on the surface of an antigen-presenting cell (APC), B cell receptors (BCRs) are gathered into microclusters that recruit signaling enzymes. These microclusters then move centripetally and coalesce into the central supramolecular activation cluster of an immune synapse. The mechanisms controlling BCR organization during immune synapse formation, and how this impacts BCR signaling, are not fully understood. We show that this coalescence of BCR microclusters depends on the actin-related protein 2/3 (Arp2/3) complex, which nucleates branched actin networks. Moreover, in murine B cells this dynamic spatial reorganization of BCR microclusters amplifies proximal BCR signaling reactions and enhances the ability of membrane-associated antigens to induce transcriptional responses and proliferation. Our finding that Arp2/3 complex activity is important for B cell responses to spatially-restricted membrane-bound antigens, but not for soluble antigens, highlights a critical role for Arp2/3 complex-dependent actin remodeling in B cell responses to APC-bound antigens.
    Keywords:  cell biology; immunology; inflammation; mouse
    DOI:  https://doi.org/10.7554/eLife.44574
  2. Polymers (Basel). 2019 Jun 04. pii: E990. [Epub ahead of print]11(6):
    Intrinsic Disorder-Based Emergence in Cellular Biology: Physiological and Pathological Liquid-Liquid Phase Transitions in Cells.
    April L Darling, Boris Y Zaslavsky, Vladimir N Uversky.
      The visible outcome of liquid-liquid phase transitions (LLPTs) in cells is the formation and disintegration of various proteinaceous membrane-less organelles (PMLOs). Although LLPTs and related PMLOs have been observed in living cells for over 200 years, the physiological functions of these transitions (also known as liquid-liquid phase separation, LLPS) are just starting to be understood. While unveiling the functionality of these transitions is important, they have come into light more recently due to the association of abnormal LLPTs with various pathological conditions. In fact, several maladies, such as various cancers, different neurodegenerative diseases, and cardiovascular diseases, are known to be associated with either aberrant LLPTs or some pathological transformations within the resultant PMLOs. Here, we will highlight both the physiological functions of cellular liquid-liquid phase transitions as well as the pathological consequences produced through both dysregulated biogenesis of PMLOs and the loss of their dynamics. We will also discuss the potential downstream toxic effects of proteins that are involved in pathological formations.
    Keywords:  intrinsically disordered protein; intrinsically disordered protein region; liquid-liquid phase transition; posttranslational modifications; protein-nucleic acid interaction; protein-protein interaction
    DOI:  https://doi.org/10.3390/polym11060990
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