DSG3 (Desmoglein 3) is a transmembrane glycoprotein belonging to the desmoglein family within the cadherin superfamily. It is a key component of desmosomes, specialized intercellular junctions that mediate strong adhesion between epithelial cells, particularly in stratified squamous epithelia such as the skin and mucous membranes. DSG3 interacts with other desmosomal proteins (e.g., desmocollins) and intracellular plakins to maintain tissue integrity by anchoring intermediate filaments to the cell membrane.
DSG3 is a major autoantigen in pemphigus vulgaris (PV), a life-threatening autoimmune blistering disorder. In PV, pathogenic IgG autoantibodies target DSG3. disrupting desmosomal adhesion and causing acantholysis (loss of cell-cell adhesion), leading to flaccid blisters and erosions on mucosal surfaces and skin. These antibodies interfere with DSG3's extracellular cadherin domains, either through steric hindrance or induction of intracellular signaling pathways that destabilize desmosomes. DSG3 autoantibodies are detected via ELISA or indirect immunofluorescence and correlate with disease activity, aiding diagnosis and monitoring.
While DSG3 is predominantly associated with PV, its expression in certain cancers (e.g., squamous cell carcinomas) has also sparked interest in its role in tumor progression and as a potential therapeutic target. Research continues to explore DSG3's pathophysiological mechanisms and its broader implications in autoimmune and oncological contexts.