Human Disease and the Desmosome

Abstract

Desmosomes are intercellular junctions of epithelia and cardiac muscle. They are located at the cell membrane where they act as anchors for intermediate filaments. Desmosomes maintain the structural integrity of tissues and disruption of desmosomal adhesion can have devastating consequences for human health. Arrhythmogenic right ventricular dysplasia, a heart muscle disease that is characterised by life‐threatening arrhythmias and increased risk of sudden heart failure, is caused by mutations in genes encoding desmosomal proteins. Other mutations can result in severe skin blistering, catastrophic fluid loss and early death. Cardiocutaneous syndromes that affect the heart, skin and hair are also caused by mutations in desmosomal genes. Pathogenic autoantibodies against desmogleins, membrane‐spanning proteins of desmosomes, cause the skin blistering diseases pemphigus and staphylococcal scalded skin syndrome. Desmosomes and their constituents could contribute to the progression of cancer. Key Concepts: Desmosomes are intercellular junctions of epithelia and cardiac muscle. Desmosomes maintain the structural integrity of tissues. Mutations in genes encoding desmosomal proteins can result in heart disease and disorders of the skin and hair. Pemphigus is an autoimmune skin blistering disease that is caused by autoantibodies against desmogleins, membrane‐spanning proteins of desmosomes. Desmosomes may be important in cancer.