desmoglein3

Desmoglein-3 is a desmosomal cadherin, a calcium-dependent cell–cell adhesion protein that is a component of desmosomes in epithelial tissues. It is encoded by the DSG3 gene. Desmoglein-3 is primarily expressed in stratified squamous epithelia, with high levels in the oral and esophageal mucosa and lower levels in native skin. It forms adhesive interactions in the intercellular space by engaging in trans interactions with desmoglein-3 molecules on neighboring cells and connects to the desmosomal plaque through intracellular proteins such as plakoglobin, plakophilins, and desmoplakin.

Desmoglein-3 has five extracellular cadherin repeats in its large extracellular domain, a single-pass transmembrane region, and a cytoplasmic tail that participates in desmosome assembly and signaling. Calcium binding is required for its adhesive function.

Functionally, Dsg3 contributes to the integrity of mucosal epithelia and to desmosomal cohesion in stratified epithelia. Its distribution helps explain tissue-specific disease patterns: Dsg3 is abundant in mucosa, whereas Dsg1 predominates in the epidermis.

Clinical significance: Autoantibodies against Dsg3 are central to pemphigus vulgaris, especially the mucosa-dominant form, causing intraepidermal blistering and mucosal erosions. In combination with antibodies to Dsg1, skin lesions are more common. Serology (ELISA for anti-Dsg3) and indirect immunofluorescence aid diagnosis and monitoring.

In research, loss or disruption of Dsg3 in animal models leads to mucosal blistering, supporting its essential role in desmosomal adhesion.