Desmoglein

Desmogleins are a subfamily of desmosomal cadherins that mediate calcium-dependent cell–cell adhesion in desmosomes. In humans, the main homologs are DSG1, DSG2, DSG3, and DSG4, expressed in tissue-specific patterns and integrated into desmosomes that contribute to the mechanical integrity of epithelia and, in some contexts, cardiac tissue.

Desmogleins are single-pass transmembrane glycoproteins with five extracellular cadherin repeats, a single transmembrane domain, and a cytoplasmic tail that binds plakoglobin and plakophilins. Through these interactions, they connect to desmoplakin and keratin intermediate filaments, forming a linkage from cell membranes to the cytoskeleton. The extracellular cadherin domains mediate calcium-dependent adhesion with neighboring cells, promoting strong intercellular junctions.

Expression and function vary by isoform: DSG1 is enriched in differentiated epidermis, DSG3 in mucosal epithelia, DSG2 more broadly expressed including cardiac tissue, and DSG4 found in certain hair-forming epithelia. Together with desmocollins, desmogleins organize desmosomes and contribute to tissue integrity and resilience against mechanical stress.

Clinical relevance highlights the importance of desmogleins in disease. Autoantibodies against desmogleins cause pemphigus: anti-DSG3 (with often anti-DSG1) in pemphigus vulgaris leads to mucocutaneous blistering, while anti-DSG1 predominates in pemphigus foliaceus. Bacterial exfoliative toxins cleave DSG1, contributing to scalded skin syndrome. Mutations in DSG2 have been linked to cardiomyopathy, illustrating a critical role in cardiac desmosomes.

Genetics and evolution: desmogleins are conserved desmosomal components with tissue-specific expression and regulation across vertebrates.