Allosteric regulation of E-cadherin adhesion

Cadherins are transmembrane adhesion proteins that maintainintercellular cohesion in all tissues, and their rapid regulationis essential for organized tissue remodeling. Despite some evidence that cadherin adhesion might be allosterically regulated, testing of this has been hindered by the difficulty of quantifyingaltered E-cadherin binding affinity caused by perturbationsoutside the ectodomain binding site. Here, measured kinetics of cadherin-mediated intercellular adhesion demonstratedquantitatively that treatment with activating, anti-Ecadherinantibodies or the dephosphorylation of a cytoplasmic binding partner, p120^ctn, increased the homophilic binding affinity of E-cadherin. Results obtained with Colo 205 cells, which express inactive E-cadherin and do not aggregate, demonstratedthat four treatments, which induced Colo 205 aggregationand p120^ctn dephosphorylation, triggered quantitatively similar increases in E-cadherin affinity. Several processes can alter cell aggregation, but these results directly demonstratedthe allosteric regulation of cell surface E-cadherin by p120^ctndephosphorylation.