Cadherin

Cadherins are a family of calcium-dependent cell–cell adhesion molecules found in animal tissues. They are transmembrane glycoproteins that mediate homophilic binding between cells and are essential for tissue architecture and morphogenesis. Classical cadherins typically consist of a single-pass transmembrane protein with an extracellular region containing multiple cadherin repeats, a single transmembrane domain, and a cytoplasmic tail that interacts with intracellular proteins. The extracellular adhesive interactions are stabilized by calcium ions.

Adhesion occurs mainly through homophilic binding of cadherins on adjacent cells, with specificity often determined by the cadherin subtype (for example, E-cadherin binds to E-cadherin on neighboring cells). The cytoplasmic domain links to the actin cytoskeleton via catenins, particularly beta-catenin or gamma-catenin and alpha-catenin, along with p120 catenin. This linkage forms the adherens junction network and coordinates cytoskeletal organization and signaling. In addition, other cadherins participate in desmosomes, such as desmogleins and desmocollins, which mediate strong cell–cell adhesion in various epithelia.

Cadherins play critical roles in development, tissue separation, wound healing, and maintenance of barrier function. They also participate in signaling pathways; for example, beta-catenin can shuttle to the nucleus and influence gene transcription in certain contexts. Non-classical cadherins and protocadherins contribute to tissue-specific adhesion and signaling complexity.

Many tissues express specific cadherins, including E-cadherin in most epithelia, N-cadherin in neural and mesenchymal tissues, VE-cadherin in endothelial cells, and P-cadherin in some epithelia. Alterations in cadherin expression or function are linked to disease, notably loss of E-cadherin in epithelial cancers, where it can promote invasion and metastasis; germline CDH1 mutations underlie hereditary diffuse gastric cancer.

In summary, cadherins are a conserved superfamily of Ca2+-dependent adhesion proteins organized into a structural and signaling network that maintains tissue integrity and regulates development.