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Desmosomes are anchoring junctions found abundantly in tissues experiencing mechanical stress, such as heart muscle and intestinal epithelium. These button-like structures form an interlinked network of intermediate filaments across cells, helping hold cells together and maintain tissue integrity under mechanical strain.

Desmosomal cadherins, namely desmocollin and desmoglein, adhere via heterophilic interactions of their extracellular domains between adjacent cells. These transmembrane glycoproteins possess a large extracellular portion comprising four cadherin repeats and one extracellular anchor domain that anchors them to the cell membrane.

Adapter proteins called plakoglobin and plakophilin bind the cytoplasmic domains of desmosomal cadherins, forming a dense plaque on the cytoplasmic side. These armadillo family proteins have characteristic arm repeats that function as docking sites for linker proteins like desmoplakin, which connects the desmosomal plaque to intermediate filaments.

Desmoplakin, the most abundant protein in a desmosomal complex, acts as a cytoskeletal linker protein belonging to the plakin family. Its N-terminal domain binds catenins while its C-terminal plakin repeats bind intermediate filaments, anchoring them across adjacent cells and forming a transcellular cytoskeletal network.

Two types of cadherins exist in desmosomes: desmogleins and desmocollins. Humans have four desmoglein isoforms and three desmocollin isoforms. Their cytoplasmic domains vary in length between different isoforms due to alternative splicing, allowing heterodimeric pairs to form clusters through cis-interactions on the same cell and trans-interactions between adjacent cells.

Desmosomal dysfunction typically manifests as disorders of the heart and skin, tissues undergoing high mechanical strain. Mutations in desmoglein genes cause epidermal thickening and arrhythmogenic right ventricular cardiomyopathy. Autoantibodies targeting desmosomal cadherins cause pemphigus vulgaris, an autoimmune disease characterized by epidermal blisters due to weak cell-cell adhesion.

Desmosomes are anchoring junctions that form a transcellular cytoskeletal network linking intermediate filaments of adjacent cells, making them essential for holding cells together under mechanical stress. This structural design allows tissues like heart muscle and intestinal epithelium to withstand continuous mechanical strain while maintaining tissue integrity.