DO ALL CADHERINS BIND THROUGH THE SAME ADHESIVE INTERFACE?

Classical cadherins are cell surface transmembrane glycoproteins involved in cell to cell adhesion. They play important roles in tissue morphogenesis and in the maintenance of tissue architecture in adults. In addition to their structural function, cadherins contacts are actively remodeled and impact cell movement and migration. Moreover, changes in cell-cell adhesion accompany the transition from benign tumor to invasive malignant cancer, and the subsequent metastatic dissemination of tumor cells. Our aim is to better understand how cadherins regulate cell contacts stability, as well as numerous intracellular signaling pathways. We choose to focus on two cadherins, E(epithelial)-cadherin that is a tumor suppressor, and cadherin-11, as prototypes of type I and type II classical cadherins respectively. Switching between E- and-11 cadherin is often observed in many epithelial cancers. Since the extracellular domain (EC) is crucial for regulating specific Ca2+-dependent homotypic interactions [1], we recombinantly expressed EC domains of E-cadherin and cadherin-11. The E-cadherin [2] and cadherin-11 (unpublished data) fragments retain biological activity when chemically immobilized on glass beads. Individual E-cadherin trans interaction was then analyzed using biophysical approaches suc