Differential Downregulation of E-Cadherin and Desmoglein by Epidermal Growth Factor

Abstract EN

Modulation of cell : cell junctions is a key event in cutaneous wound repair.

In this study we report that activation of the epidermal growth factor (EGF) receptor disrupts cell : cell adhesion, but with different kinetics and fates for the desmosomal cadherin desmoglein and for E-cadherin.

Downregulation of desmoglein preceded that of E-cadherin in vivo and in an EGF-stimulated in vitro wound reepithelialization model.

Dual immunofluorescence staining revealed that neither E-cadherin nor desmoglein-2 internalized with the EGF receptor, or with one another.

In response to EGF, desmoglein-2 entered a recycling compartment based on predominant colocalization with the recycling marker Rab11.

In contrast, E-cadherin downregulation was accompanied by cleavage of the extracellular domain.

A broad-spectrum matrix metalloproteinase inhibitor protected E-cadherin but not the desmosomal cadherin, desmoglein-2, from EGF-stimulated disruption.

These findings demonstrate that although activation of the EGF receptor regulates adherens junction and desmosomal components, this stimulus downregulates associated cadherins through different mechanisms.