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Cited by 32Microtubule and mitosis dynamicsDevelopmental Biology and Gene RegulationCellular Mechanics and Interactions

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Synthetic Par polarity induces cytoskeleton asymmetry in unpolarized mammalian cells

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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·2023·Cell
DOI 10.1016/j.cell.2023.08.034PMC PMC10765089

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Abstract

Abstract Polarized cells rely on a polarized cytoskeleton for polarized trafficking, oriented migration and spindle orientation during asymmetric cell division. While cytoskeleton remodeling machineries have been extensively characterized at the molecular level, how polarity signaling at the cortex controls remodeling of the cytoskeleton in the cytosol remains elusive. In particular, how the Par complex, the conserved mastermind of polarity during asymmetric cell division, gets assembled and functions is not understood at the molecular level. Here, we dissected the logic of the Par complex pathway by capitalizing on designed proteins able to induce spontaneous symmetry breaking of the cortex in populations of naïve, unpolarized cells. We found that the primary kinetic barrier to Par complex assembly is the relief of Par6 autoinhibition, and that inducing Par complex cortical polarity was sufficient to induce two key hallmarks of asymmetric cell division in unpolarized cells: spindle orientation and central spindle asymmetry. These two outputs of the Par complex are separately controlled: spindle orientation is determined by Par3 and does not require the kinase activity of aPKC, while central spindle asymmetry solely depends on an asymmetric activity of aPKC at the cortex. Our work shows how polarity information flows between the cortex and the cytosol despite its diffusive nature, and paves the way towards induction of asymmetric cell division in cultured cells.

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Metadata

Authors
Watson, J. L., Krüger, L. K., Ben-Sasson, A. J., Bittleston, A., Shahbazi, M. N., Planelles-Herrero, V. J., Chambers, J. E., Manton, J. D., Baker, D., & Derivery, E.
Affiliations
  • MRC Laboratory of Molecular Biology (GB)
  • University of Cambridge (GB)
  • Howard Hughes Medical Institute (US)
Corresponding author
Derivery, Emmanuel
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2023-10
Volume
186
Issue
21
Pages
4710-4727.e35
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2023.08.034
PMC
PMC10765089
OpenAlex
W4387131807
Cited by
32
References
3
Citations by year
2026: 9 · 2025: 9 · 2024: 14
FWCI
4.63
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • Wellcome Trust (100140)
  • Medical Research Council (MR/V028669/1, MC_UP_1201/13)
  • Cambridge Institute for Medical Research, University of Cambridge (100140)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
Par complex, cortical polarity, asymmetric cell division, Par3, atypical protein kinase C, spindle orientation, mitosis, mammalian cells
MeSH terms
Animals, Cytological Techniques, Cytoskeleton, Mammals, Microtubules, Mitosis, Protein Kinase C, Cell Polarity, Adaptor Proteins, Signal Transducing

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