title: Binding of cadmium (Cd2+) to E-CAD1, a calcium-binding polypeptide analog of E-cadherin.
abstract: Recent studies have shown that Cd2+ can damage the Ca(2+)-dependent junctions between renal epithelial cells in culture, and preliminary evidence suggests that this effect may involve the interaction of Cd2+ with E-cadherin, a Ca(2+)-dependent cell adhesion molecule that is localized at the adhering junctions of epithelial cells. To determine whether or not Cd2+ might bind directly to the E-cadherin molecule, we studied the binding of Cd2+ to E-CAD1, a recombinant, 145-residue polypeptide that corresponds to one of the extracellular Ca(2+)-binding regions of mouse E-cadherin. By using an equilibrium microdialysis technique, we were able to show that Cd2+ could, in fact, bind to E-CAD1. The binding was saturable, with a maximum of one Cd2+ binding site per E-CAD1 molecule. The apparent dissociation constant (KD) for the binding was about 20 microM, a concentration similar to that which has been shown to disrupt the junctions between epithelial cells. Other results showed that the binding of CD2+ was greatly reduced when excess Ca2+ was included in the dialysis solution. These results suggest that Cd2+ can interact with the Ca2+ binding regions on the E-CAD1 molecule, and they provide additional support for the hypothesis that E-cadherin might be a molecular target for Cd2+ toxicity.
authors.affiliation: Department of Pharmacology, Midwestern University, Downers Grove, IL 60515, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Prozialeck
authors.forename: P C
authors.initials: PC
authors.lastname: Lamar
authors.forename: M
authors.initials: M
authors.lastname: Ikura
mesh_terms: D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002104:Cadmium / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D011485:Protein Binding
chemical_list: D015820:Cadherins; D002104:Cadmium; D002118:Calcium