Reevaluating αE-catenin monomer and homodimer functions by characterizing E-cadherin/αE-catenin chimeras

As part of the E-cadherin-beta-catenin-alpha E-catenin complex (CCC), mammalian alpha E-catenin binds F-actin weakly in the absence of force, whereas cytosolic alpha E-catenin forms a homodimer that interacts more strongly with F-actin. It has been concluded that cytosolic alpha E-catenin homodimer is not important for intercellular adhesion because E-cadherin/alpha E-catenin chimeras thought to mimic the CCC are sufficient to induce cell cell adhesion. We show that, unlike alpha E-catenin in the CCC, these chimeras homodimerize, bind F-actin strongly, and inhibit the Arp2/3 complex, all of which are properties of the alpha E-catenin homodimer. To more accurately mimic the junctional CCC, we designed a constitutively monomeric chimera, and show that E-cadherin dependent cell adhesion is weaker in cells expressing this chimera compared with cells in which alpha E-catenin homodimers are present. Our results demonstrate that E-cadherin/alpha E-catenin chimeras used previously do not mimic alpha E-catenin in the native CCC, and imply that both CCC-bound monomer and cytosolic homodimer alpha E-catenin are required for strong cell-cell adhesion.