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.
Department of Tissue Development and Regeneration, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, S-1, W-17, Chuo-ku, Sapporo 060-8556, Japan. Electronic address: hirotake@sapmed.ac.jp.
Hiroshi
H
Takeda
D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002104:Cadmium / Q000378:metabolism* / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004785:Environmental Pollutants / Q000378:metabolism* / Q000633:toxicity; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D055503:Protein Multimerization / Q000187:drug effects
D015820:Cadherins; D002413:Cations, Divalent; D004785:Environmental Pollutants; D002104:Cadmium; D002118:Calcium
Cadherin; Cadmium; Calcium; Cell–cell adhesion; cis-Dimer