Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity

Nat Commun. 2017 Jan 13;8:13998. doi: 10.1038/ncomms13998.

Abstract

Monolayered epithelia are composed of tight cell assemblies that ensure polarized exchanges. EpCAM, an unconventional epithelial-specific cell adhesion molecule, is assumed to modulate epithelial morphogenesis in animal models, but little is known regarding its cellular functions. Inspired by the characterization of cellular defects in a rare EpCAM-related human intestinal disease, we find that the absence of EpCAM in enterocytes results in an aberrant apical domain. In the course of this pathological state, apical translocation towards tricellular contacts (TCs) occurs with striking tight junction belt displacement. These unusual cell organization and intestinal tissue defects are driven by the loss of actomyosin network homoeostasis and contractile activity clustering at TCs, yet is reversed by myosin-II inhibitor treatment. This study reveals that adequate distribution of cortical tension is crucial for individual cell organization, but also for epithelial monolayer maintenance. Our data suggest that EpCAM modulation protects against epithelial dysplasia and stabilizes human tissue architecture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / chemistry
  • Actomyosin / genetics
  • Actomyosin / metabolism
  • Adolescent
  • Biomechanical Phenomena
  • Caco-2 Cells
  • Cell Polarity
  • Child
  • Child, Preschool
  • Diarrhea, Infantile / genetics
  • Diarrhea, Infantile / metabolism
  • Enterocytes / chemistry
  • Enterocytes / metabolism
  • Epithelial Cell Adhesion Molecule / chemistry
  • Epithelial Cell Adhesion Molecule / genetics
  • Epithelial Cell Adhesion Molecule / metabolism
  • Epithelial Cells / chemistry*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelium / chemistry*
  • Epithelium / metabolism
  • Female
  • Humans
  • Infant
  • Malabsorption Syndromes / genetics
  • Malabsorption Syndromes / metabolism
  • Male
  • Tight Junctions / chemistry
  • Tight Junctions / genetics
  • Tight Junctions / metabolism

Substances

  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Actomyosin

Supplementary concepts

  • Diarrhea 5, With Tufting Enteropathy, Congenital