Regulation of keratinocyte intercellular junction organization and epidermal morphogenesis by E-cadherin.

Elevation of the calcium concentration in human keratinocyte culture rapidly induces the redistribution of E-cadherin, P-cadherin, vinculin, beta 1 integrin, and desmoplakin to the cell-cell borders. Antibody to E-cadherin that blocks its functional activity delays the redistribution of each marker by several hours. Furthermore, antibody to E-cadherin interferes with normal, calcium-induced stratification of keratinocytes. Although several uneven vertical layers of cells can be detected in the presence of anti-E-cadherin antibody, the superficial cells appear defective in their adhesion. They do not flatten upon the basal layer nor do they enlarge, as do the controls; but rather they remain in groups of small cells connected by a line of single cells or by very long processes. In spite of the deformed appearance of the superficial cells in the presence of anti-E-cadherin IgG, these cells express the differentiation marker filaggrin, do not express P-cadherin, and concentrate desmoplakin at their cell-cell borders, consistent with the pattern in normally stratified cultures and in epidermis. These studies suggest a central role for E-cadherin in the regulation of keratinocyte intercellular junction organization as well as in epidermal morphogenesis.