bims-fascar Biomed News
on Phase separation and cellular architecture
Issue of 2019‒06‒16
two papers selected by
Victoria Yan
Max Planck Institute of Molecular Cell Biology and Genetics


  1. Curr Opin Cell Biol. 2019 Jun 05. pii: S0955-0674(19)30041-9. [Epub ahead of print]60 92-98
    Tiwary AK, Zheng Y.
      Through phase separation, some proteins form liquid-like condensates or droplets which can flow, fuse, and even deform when pressure is applied. In some cases, the condensates 'mature' to form gel or solid-like structure. Recent studies suggest that the liquid-like condensates form the structural basis for several membrane-less subcellular organelles such as stress granules and other subcellular structures. Here, we review and discuss studies that implicate protein phase separation in the function of the spindle apparatus and centrosomes.
    DOI:  https://doi.org/10.1016/j.ceb.2019.04.011
  2. Proc Natl Acad Sci U S A. 2019 Jun 12. pii: 201818808. [Epub ahead of print]
    McCall PM, MacKintosh FC, Kovar DR, Gardel ML.
      The shape of most animal cells is controlled by the actin cortex, a thin network of dynamic actin filaments (F-actin) situated just beneath the plasma membrane. The cortex is held far from equilibrium by both active stresses and polymer turnover: Molecular motors drive deformations required for cell morphogenesis, while actin-filament disassembly dynamics relax stress and facilitate cortical remodeling. While many aspects of actin-cortex mechanics are well characterized, a mechanistic understanding of how nonequilibrium actin turnover contributes to stress relaxation is still lacking. To address this, we developed a reconstituted in vitro system of entangled F-actin, wherein the steady-state length and turnover rate of F-actin are controlled by the actin regulatory proteins cofilin, profilin, and formin, which sever, recycle, and assemble filaments, respectively. Cofilin-mediated severing accelerates the turnover and spatial reorganization of F-actin, without significant changes to filament length. We demonstrate that cofilin-mediated severing is a single-timescale mode of stress relaxation that tunes the low-frequency viscosity over two orders of magnitude. These findings serve as the foundation for understanding the mechanics of more physiological F-actin networks with turnover and inform an updated microscopic model of single-filament turnover. They also demonstrate that polymer activity, in the form of ATP hydrolysis on F-actin coupled to nucleotide-dependent cofilin binding, is sufficient to generate a form of active matter wherein asymmetric filament disassembly preserves filament number despite sustained severing.
    Keywords:  active matter; cell mechanics; cytoskeleton; microrheology; nonequilibrium
    DOI:  https://doi.org/10.1073/pnas.1818808116