desmosomes

Desmosomes are cell–cell junctions that provide strong adhesion between neighboring cells, particularly in tissues subjected to mechanical stress such as the epidermis and heart. They help tissues withstand stretching and pulling forces by distributing mechanical load across cells.

Structurally, desmosomes are built from transmembrane cadherins, mainly desmogleins and desmocollins, whose extracellular domains engage in adhesive interactions with cadherins on adjacent cells. The cytoplasmic tails bind to desmosomal plaque proteins, including desmoplakin, plakoglobin, and plakophilins, which connect to the intermediate filament cytoskeleton (keratin in epithelia, desmin in cardiac muscle). This arrangement anchors cells to one another and to the cytoskeleton.

Desmosome formation is calcium-dependent. Adhesion begins with intercellular cadherin interactions and proceeds to plaque assembly that links to intermediate filaments, yielding a robust mechanical connection that helps tissues maintain integrity during mechanical stress.

Clinical relevance is notable. Autoimmune diseases such as pemphigus vulgaris and pemphigus foliaceus involve antibodies against desmogleins, leading to loss of cell–cell adhesion and blistering. Genetic mutations in desmosomal components, including DSP, DSG2, DSC2, and PKP2, are associated with cardiomyopathies and skin disorders, underscoring the importance of desmosomes in tissue function.

Desmosomes also participate in signaling networks and can influence cellular behavior beyond adhesion. Their composition and dynamics are regulated during development, wound healing, and tissue maintenance, reflecting their integral role in tissue architecture and homeostasis.