UC San Diego

The epidermis is a continually regenerating epithelial tissue that relies on a stringently regulated balance between proliferation and differentiation. As the proliferative stem cells within the basal layer of the epidermis transition through the suprabasal layers towards the surface of the skin, the cells lose their self- renewing ability and terminally differentiate. E-cadherin is a transmembrane protein that mediates intercellular adhesion through binding catenin family proteins to the actin cytoskeleton and has been shown to play a role in differentiation but its importance and the precise mechanism is unknown. To determine which domain of E- cadherin is sufficient to induce differentiation, chimeric E-cadherin constructs were expressed in keratinocytes. Luciferase reporter gene assays showed that all constructs that have the p120-catenin binding induced differentiation. The p120-catenin binding domain alone was sufficient to induce differentiation suggesting that the p120-cetnin binding domain is both necessary and sufficient to induce differentiation. When p120-catenin was overexpressed, it was able to rescue the phenotype caused by the p120-catenin binding domain. Findings were validated by qPCR of endogenous keratin 10 expression. This suggests that p120-catenin sequestration by E- cadherin to the plasma membrane leading to epidermal stem cell differentiation may be due to a depletion of nuclear p120-catenin. Furthermore, of the different isoforms of p120-catenin, isoform A was determined to be the most abundant in keratinocytes