desmosome

A desmosome, also known as a macula adherens, is a cell–cell junction that provides strong mechanical adhesion between neighboring cells. It is especially abundant in tissues subjected to large forces, such as the epidermis and the cardiac muscle, where it helps maintain tissue integrity during contraction and stretching.

Desmosomes are composed of transmembrane cadherin proteins, primarily desmogleins (DSG) and desmocollins (DSC), which form calcium-dependent adhesive links across the extracellular space. The inner cytoplasmic plaque contains a network of proteins, including desmoplakin, plakoglobin (gamma-catenin), and plakophilins, which connect the cadherins to the cell’s intermediate filament system (keratins in epithelia; desmin in cardiac muscle).

Mechanically, desmosomes anchor the intermediate filament networks of adjoining cells to form robust adhesive complexes. This arrangement distributes tensile stress across a tissue and helps cells resist shear forces. Desmosomes are distinct from adherens junctions, which link cadherins to actin filaments; desmosomes specifically interface with intermediate filaments, providing durable cell–cell attachment.

Clinical significance and disorders:

Genetic mutations in desmosomal components (such as desmoplakin, plakophilins, desmogleins, and desmocollins) can lead to cardiomyopathies, notably arrhythmogenic right ventricular cardiomyopathy, and related syndromes. Autoimmune targeting of desmosomal cadherins, especially desmogleins, causes bullous autoimmune diseases such as pemphigus vulgaris and pemphigus foliaceus, characterized by loss of cell adhesion (acantholysis). Naxos disease represents a syndromic form with cardiomyopathy and skin manifestations linked to desmosomal gene mutations.