Modulation of cell : cell junctions is a key event in cutaneous wound repair. In this study we report that activation of the epidermal\r\ngrowth factor (EGF) receptor disrupts cell : cell adhesion, but with different kinetics and fates for the desmosomal cadherin\r\ndesmoglein and for E-cadherin. Downregulation of desmoglein preceded that of E-cadherin in vivo and in an EGF-stimulated\r\nin vitro wound reepithelialization model. Dual immunofluorescence staining revealed that neither E-cadherin nor desmoglein-\r\n2 internalized with the EGF receptor, or with one another. In response to EGF, desmoglein-2 entered a recycling compartment\r\nbased on predominant colocalization with the recycling marker Rab11. In contrast, E-cadherin downregulation was accompanied\r\nby cleavage of the extracellular domain. A broad-spectrum matrix metalloproteinase inhibitor protected E-cadherin but not the\r\ndesmosomal cadherin, desmoglein-2, from EGF-stimulated disruption. These findings demonstrate that although activation of\r\nthe EGF receptor regulates adherens junction and desmosomal components, this stimulus downregulates associated cadherins\r\nthrough different mechanisms.
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