bims-fascar Biomed News
on Phase separation and cellular architecture
Issue of 2021–02–28
two papers selected by
Victoria Tianjing Yan, Max Planck Institute of Molecular Cell Biology and Genetics
  1. Phase separation-mediated condensation of Whirlin-Myo15-Eps8 stereocilia tip complex.
  2. Should I bend or should I grow: the mechanisms of droplet-mediated autophagosome formation.
  1. Cell Rep. 2021 Feb 23. pii: S2211-1247(21)00083-8. [Epub ahead of print]34(8): 108770
    Phase separation-mediated condensation of Whirlin-Myo15-Eps8 stereocilia tip complex.
    Lin Lin, Yingdong Shi, Mengli Wang, Chao Wang, Qing Lu, Jinwei Zhu, Rongguang Zhang.
      Stereocilia, the mechanosensory organelles on the apical surface of hair cells, are necessary to detect sound and carry out mechano-electrical transduction. An electron-dense matrix is located at the distal tips of stereocilia and plays crucial roles in the regulation of stereocilia morphology. Mutations of the components in this tip complex density (TCD) have been associated with profound deafness. However, the mechanism underlying the formation of the TCD is largely unknown. Here, we discover that the specific multivalent interactions among the Whirlin-myosin 15 (Myo15)-Eps8 complex lead to the formation of the TCD-like condensates through liquid-liquid phase separation. The reconstituted TCD-like condensates effectively promote actin bundling. A deafness-associated mutation of Myo15 interferes with the condensates formation and consequently impairs actin bundling. Therefore, our study not only suggests that the TCD in hair cell stereocilia may form via phase separation but it also provides important clues for the possible mechanism underlying hearing loss.
    Keywords:  actin bundling; phase separation; stereocilia; tip complex; usher syndrome; whirlin
    DOI:  https://doi.org/10.1016/j.celrep.2021.108770
  2. Autophagy. 2021 Feb 25. 1-3
    Should I bend or should I grow: the mechanisms of droplet-mediated autophagosome formation.
    Sebastian W Schultz, Jaime Agudo-Canalejo, Haruka Chino, Simona M Migliano, Chieko Saito, Ikuko Koyama-Honda, Harald Stenmark, Andreas Brech, Noboru Mizushima, Roland L Knorr, Alexander I May.
      Phase-separated droplets with liquid-like properties can be degraded by macroautophagy/autophagy, but the mechanism underlying this degradation is poorly understood. We have recently derived a physical model to investigate the interaction between autophagic membranes and such droplets, uncovering that intrinsic wetting interactions underlie droplet-membrane contacts. We found that the competition between droplet surface tension and the increasing tendency of growing membrane sheets to bend determines whether a droplet is completely engulfed or isolated in a piecemeal fashion, a process we term fluidophagy. Intriguingly, we found that another critical parameter of droplet-membrane interactions, the spontaneous curvature of the membrane, determines whether the droplet is degraded by autophagy or - counterintuitively - serves as a platform from which autophagic membranes expand into the cytosol. We also discovered that the interaction of membrane-associated LC3 with the LC3-interacting region (LIR) found in the autophagic cargo receptor protein SQSTM1/p62 and many other autophagy-related proteins influences the preferred bending directionality of forming autophagosomes in living cells. Our study provides a physical account of how droplet-membrane wetting underpins the structure and fate of forming autophagosomes.
    Keywords:  Autophagy; condensate; droplet; isolation membrane; membrane; p62; phase separation; piecemeal autophagy; wetting
    DOI:  https://doi.org/10.1080/15548627.2021.1887548
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