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Synthetic Par polarity induces cytoskeleton asymmetry in unpolarized mammalian cells.
Watson, Joseph L; Krüger, Lara K; Ben-Sasson, Ariel J; Bittleston, Alice; Shahbazi, Marta N; Planelles-Herrero, Vicente Jose; Chambers, Joseph E; Manton, James D; Baker, David; Derivery, Emmanuel.
Affiliation
  • Watson JL; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
  • Krüger LK; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
  • Ben-Sasson AJ; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Bittleston A; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
  • Shahbazi MN; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
  • Planelles-Herrero VJ; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
  • Chambers JE; Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Hills Rd, Cambridge, UK.
  • Manton JD; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
  • Baker D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
  • Derivery E; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK. Electronic address: derivery@mrc-lmb.cam.ac.uk.
Cell ; 186(21): 4710-4727.e35, 2023 10 12.
Article in En | MEDLINE | ID: mdl-37774705
ABSTRACT
Polarized cells rely on a polarized cytoskeleton to function. Yet, how cortical polarity cues induce cytoskeleton polarization remains elusive. Here, we capitalized on recently established designed 2D protein arrays to ectopically engineer cortical polarity of virtually any protein of interest during mitosis in various cell types. This enables direct manipulation of polarity signaling and the identification of the cortical cues sufficient for cytoskeleton polarization. Using this assay, we dissected the logic of the Par complex pathway, a key regulator of cytoskeleton polarity during asymmetric cell division. We show that cortical clustering of any Par complex subunit is sufficient to trigger complex assembly and that the primary kinetic barrier to complex assembly is the relief of Par6 autoinhibition. Further, we found that inducing cortical Par complex polarity induces two hallmarks of asymmetric cell division in unpolarized mammalian cells spindle orientation, occurring via Par3, and central spindle asymmetry, depending on aPKC activity.
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Full text: 1 Database: MEDLINE Main subject: Cytological Techniques / Cell Polarity / Adaptor Proteins, Signal Transducing / Mitosis Limits: Animals Language: En Year: 2023 Type: Article

Full text: 1 Database: MEDLINE Main subject: Cytological Techniques / Cell Polarity / Adaptor Proteins, Signal Transducing / Mitosis Limits: Animals Language: En Year: 2023 Type: Article