Effects of Cd2+ on cis-dimer structure of E-cadherin in living cells

E-cadherin, a calcium (Ca(2+))-dependent cell-cell adhesion molecule, plays a key role in the maintenance of tissue integrity. We have previously demonstrated that E-cadherin functions in vivo as a cis-dimer through chemical cross-linking reagents. Ca(2+) plays an important role in the cis-dimer formation of cadherin. However, the molecular mechanisms by which Ca(2+) interacts with the binding sites that regulate cis-dimer structures have not been completely elucidated. As expected for a Ca(2+) antagonist, cadmium (Cd(2+)) disrupts cadherin function by displacing Ca(2+) from its binding sites on the cadherin molecules. We used Cd(2+) as a probe for investigating the role of Ca(2+) in the dynamics of the E-cadherin extracellular region that involve cis-dimer formation and adhesion. While cell-cell adhesion assembly was completely disrupted in the presence of Cd(2+), the amount of cis-dimers of E-cadherin that formed at the cell surface was not affected. In our "Cd(2+)-switch" experiments, we did not find that Cd(2+)-induced E-cadherin cis-dimer formation in EL cells when they were incubated in low-Ca(2+) medium. In the present study, we demonstrated for the first time the effects of Cd(2+) on the cis-dimer structure of E-cadherin in living cells using a chemical cross-link analysis.