Cadherins

Cadherins are a family of calcium-dependent transmembrane proteins that mediate homophilic cell–cell adhesion and form the core of adherens junctions in many animal tissues. They are characterized by a single membrane-spanning region and a extracellular region composed of multiple cadherin repeats, which mediate calcium-dependent binding between neighboring cells. Classical cadherins, such as E-cadherin (CDH1), N-cadherin (CDH2), P-cadherin (CDH3), and VE-cadherin (CDH5), play key roles in maintaining tissue architecture, polarity, and communication.

Adhesion is typically homophilic, meaning cadherins of the same type on adjacent cells bind each other. The extracellular cadherin repeats require calcium ions to maintain a rigid conformation necessary for adhesive interactions. The cytoplasmic tail binds catenin proteins (including beta-catenin, alpha-catenin, and p120-catenin), linking the cadherin complex to the actin cytoskeleton and thereby coordinating adhesion with the cytoskeleton and signaling pathways. This linkage enables junctional remodeling during development, wound healing, and tissue maintenance.

Cadherins contribute to tissue sorting and morphogenesis, with differential expression guiding cell movements and boundary formation. Desmosomal cadherins (desmogleins and desmocollins) participate in desmosomes, providing strong cell–cell adhesion in tissues subjected to mechanical stress.

Dysregulation of cadherins, particularly E-cadherin, is linked to disease. Loss or suppression of E-cadherin promotes epithelial-to-mesenchymal transition and metastasis in cancer. Mutations in CDH1 are associated with hereditary diffuse gastric cancer and other pathologies.