Apico-basal cell compression regulates Lamin A/C levels in epithelial tissues

Nat Commun. 2021 Mar 25;12(1):1756. doi: 10.1038/s41467-021-22010-9.

Abstract

The levels of nuclear protein Lamin A/C are crucial for nuclear mechanotransduction. Lamin A/C levels are known to scale with tissue stiffness and extracellular matrix levels in mesenchymal tissues. But in epithelial tissues, where cells lack a strong interaction with the extracellular matrix, it is unclear how Lamin A/C is regulated. Here, we show in epithelial tissues that Lamin A/C levels scale with apico-basal cell compression, independent of tissue stiffness. Using genetic perturbations in Drosophila epithelial tissues, we show that apico-basal cell compression regulates the levels of Lamin A/C by deforming the nucleus. Further, in mammalian epithelial cells, we show that nuclear deformation regulates Lamin A/C levels by modulating the levels of phosphorylation of Lamin A/C at Serine 22, a target for Lamin A/C degradation. Taken together, our results reveal a mechanism of Lamin A/C regulation which could provide key insights for understanding nuclear mechanotransduction in epithelial tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleus / physiology*
  • Dogs
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Epithelium / metabolism
  • Lamin Type A / genetics
  • Lamin Type A / metabolism*
  • Lamins / genetics
  • Lamins / metabolism*
  • Madin Darby Canine Kidney Cells
  • Mechanotransduction, Cellular / physiology*
  • Phosphorylation
  • Stress, Mechanical*

Substances

  • Drosophila Proteins
  • LamC protein, Drosophila
  • Lamin Type A
  • Lamins