Functional Implications of the Interaction Between the Tetraspanin CD82/KAI1 and Adherens Junction Proteins

The establishment and maintenance of selective permeability barriers in epithelia is critically dependent upon cell-cell contacts among neighboring epithelial cells. Several human diseases, including cancer, have been linked to disruption or aberrant functioning of cellular adhesion mechanisms. The tetraspanin superfamily is an emerging family of glycoproteins that are involved in numerous biological processes including cell adhesion, fusion, migration, and proliferation; synapse formation; and neurite outgrowth. Although several lines of evidence support the idea that the tetraspanin CD82 functions as an inhibitor of metastatic cell behavior, there is a dearth of information regarding whether CD82 interacts with proteins resident at the adherens junction or its downstream signaling components and what the functional significance of these interactions may be. We sought to address these issues through the use of various established cellular and molecular biology techniques. We were able to demonstrate stable interactions between CD82 and two components of the adherens junction, E-cadherin and beta-catenin, as well as establish an inhibitory effect of CD82 on beta-catenin signaling and provide evidence for a regulatory role of CD82 in the proteolytic processing of E-cadherin. Our work extends our understanding of tetraspanins as molecular facilitators and may ultimately be useful in designing new cancer therapeutics.