A Novel Regulatory Pathway of Desmoglein-3 in Keratinocyte Stress Response

Abstract

Desmoglein-3 (Dsg3) belongs to a subfamily of the desmosomal cadherins and is an essential component of the junctional protein complex known as the desmosome that mediates calcium-dependent cell-cell adhesion in vertebrate epithelial cells [1]. Desmosomes occur in abundance in tissues, such as the skin and mucous membrane that are subjected to extensive mechanical stress. In addition to its role in cell-cell adhesion, Dsg3 also functions as a surface regulator for various intracellular signaling pathways in epithelial cells [1-7]. Many of these findings are achieved from the studies of the pathogenesis of Pemphigus Vulgaris (PV), an autoimmune bullous disease in which Dsg3 serves as a major autoantigen and is targeted by circulating autoantibodies that cause disruption of desmosomes, resulting in blistering affecting both the skin and mucous membrane [2,3,6]. This minireview will focus on our recent findings suggesting an unprecedented signaling role of Dsg3 in regulating two fundamental pathways that control cell proliferation and cell fate decision [8,9]. The involvement of this pathway in the pathogenesis of PV is also discussed briefly in this review.