The zonula adherens matura redefines the apical junction of intestinal epithelia

Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2316722121. doi: 10.1073/pnas.2316722121. Epub 2024 Feb 20.

Abstract

Cell-cell apical junctions of epithelia consist of multiprotein complexes that organize as belts regulating cell-cell adhesion, permeability, and mechanical tension: the tight junction (zonula occludens), the zonula adherens (ZA), and the macula adherens. The prevailing dogma is that at the ZA, E-cadherin and catenins are lined with F-actin bundles that support and transmit mechanical tension between cells. Using super-resolution microscopy on human intestinal biopsies and Caco-2 cells, we show that two distinct multiprotein belts are basal of the tight junctions as the intestinal epithelia mature. The most apical is populated with nectins/afadin and lined with F-actin; the second is populated with E-cad/catenins. We name this dual-belt architecture the zonula adherens matura. We find that the apical contraction apparatus and the dual-belt organization rely on afadin expression. Our study provides a revised description of epithelial cell-cell junctions and identifies a module regulating the mechanics of epithelia.

Keywords: actin cytoskeleton; adhesive complexes; epithelial cells; small intestine; zonula adherens.

MeSH terms

  • Actins* / metabolism
  • Adherens Junctions* / metabolism
  • Caco-2 Cells
  • Cadherins / genetics
  • Cadherins / metabolism
  • Catenins / metabolism
  • Epithelial Cells / metabolism
  • Humans
  • Intercellular Junctions / metabolism
  • Tight Junctions / metabolism

Substances

  • Actins
  • Cadherins
  • Catenins