bims-fascar Biomed News
on Phase separation and cellular architecture
Issue of 2019–07–07
two papers selected by
Victoria Tianjing Yan, Max Planck Institute of Molecular Cell Biology and Genetics
  1. A composition-dependent molecular clutch between T cell signaling condensates and actin.
  2. Biomolecular condensation of the microtubule-associated protein tau.
  1. Elife. 2019 Jul 03. pii: e42695. [Epub ahead of print]8
    A composition-dependent molecular clutch between T cell signaling condensates and actin.
    Jonathon A Ditlev, Anthony R Vega, Darius Vasco Köster, Xiaolei Su, Tomomi Tani, Ashley M Lakoduk, Ronald D Vale, Satyajit Mayor, Khuloud Jaqaman, Michael K Rosen.
      During T cell activation, biomolecular condensates form at the immunological synapse (IS) through multivalency-driven phase separation of LAT, Grb2, Sos1, SLP-76, Nck, and WASP. These condensates move radially at the IS, traversing successive radially-oriented and concentric actin networks. To understand this movement, we biochemically reconstituted LAT condensates with actomyosin filaments. We found that basic regions of Nck and N-WASP/WASP promote association and co-movement of LAT condensates with actin, indicating conversion of weak individual affinities to high collective affinity upon phase separation. Condensates lacking these components were propelled differently, without strong actin adhesion. In cells, LAT condensates lost Nck as radial actin transitioned to the concentric network, and engineered condensates constitutively binding actin moved aberrantly. Our data show that Nck and WASP form a clutch between LAT condensates and actin in vitro and suggest that compositional changes may enable condensate movement by distinct actin networks in different regions of the IS.
    Keywords:  biochemistry; cell biology; chemical biology; human
    DOI:  https://doi.org/10.7554/eLife.42695
  2. Semin Cell Dev Biol. 2019 Jun 28. pii: S1084-9521(18)30199-X. [Epub ahead of print]
    Biomolecular condensation of the microtubule-associated protein tau.
    Tina Ukmar-Godec, Susanne Wegmann, Markus Zweckstetter.
      Cells contain multiple compartments dedicated to the regulation and control of biochemical reactions. Cellular compartments that are not surrounded by membranes can rapidly form and dissolve in response to changes in the cellular environment. The physicochemical processes that underlie the formation of non-membrane-bound compartments in vivo are connected to liquid-liquid phase separation of proteins and nucleic acids in vitro. Recent evidence suggests that the protein tau, which plays an important role in Alzheimer's disease and other neurodegenerative disorders, phase separates in solution, forms tau phases with microtubules, and associates with phase-separated RNA-binding protein granules in cells. Here we review the experimental evidence that supports the ability of tau to phase separate in solution and form biomolecular condensates in cells. As for other disease-relevant proteins, the physiological and pathological functions of tau are tightly connected - through loss of normal function or gain of toxic function - and we therefore discuss how tau phase separation plays a role for both, and with respect to different cellular functions of tau.
    Keywords:  liquid-liquid phase separation; neurodegeneration; post-translational modifications; stress granule; tau protein
    DOI:  https://doi.org/10.1016/j.semcdb.2019.06.007
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