Nectins rather than E-cadherin anchor the actin belts at cell-cell junctions of epithelia

Cell-cell junctions support the mechanical integrity of epithelia by enabling adhesion and tension transmission between neighboring cells. The prevailing mechanistic dogma is that E-cadherin supports and transmits mechanical tension between cells through actin belts in a region named the zonula adherens. Using super-resolution microscopy on human intestinal biopsies and Caco-2 cells, we show that the zonula adherens consists of E-cadherin and nectin belts that are separated by about 150 nm along the apico-basal direction, the nectin belt being in the immediate vicinity of the actin belt. The segregation of nectins and E-cadherin increases as the tissue matures. Our data redefine the structure of the zonula adherens and show that nectins, rather than E-cadherin, are the major connectors of actin belts in epithelia.