F-Actin Interactome Reveals Vimentin as a Key Regulator of Actin Organization and Cell Mechanics in Mitosis

Dev Cell. 2020 Jan 27;52(2):210-222.e7. doi: 10.1016/j.devcel.2019.12.011. Epub 2020 Jan 9.

Abstract

Most metazoan cells entering mitosis undergo characteristic rounding, which is important for accurate spindle positioning and chromosome separation. Rounding is driven by contractile tension generated by myosin motors in the sub-membranous actin cortex. Recent studies highlight that alongside myosin activity, cortical actin organization is a key regulator of cortex tension. Yet, how mitotic actin organization is controlled remains poorly understood. To address this, we characterized the F-actin interactome in spread interphase and round mitotic cells. Using super-resolution microscopy, we then screened for regulators of cortex architecture and identified the intermediate filament vimentin and the actin-vimentin linker plectin as unexpected candidates. We found that vimentin is recruited to the mitotic cortex in a plectin-dependent manner. We then showed that cortical vimentin controls actin network organization and mechanics in mitosis and is required for successful cell division in confinement. Together, our study highlights crucial interactions between cytoskeletal networks during cell division.

Keywords: CDK1; actin organization; cell shape; cortex; mitosis; mitotic rounding; phosphorylation; plectin; proteomics; vimentin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / physiology*
  • Actins / metabolism*
  • Cell Physiological Phenomena*
  • Chromosome Segregation
  • HeLa Cells
  • Humans
  • Intermediate Filaments / physiology*
  • Interphase / physiology*
  • Mitosis*
  • Vimentin / metabolism*

Substances

  • Actins
  • Vimentin