cadherinfamily

The cadherin family comprises calcium-dependent transmembrane proteins that mediate cell–cell adhesion in a wide range of tissues. They function as homophilic adhesion molecules, meaning a cadherin on one cell binds to the same type of cadherin on a neighboring cell. Cadherins are characterized by extracellular cadherin repeats, a single transmembrane region, and a cytoplasmic tail that connects to the actin cytoskeleton through catenins, allowing both mechanical cohesion and signaling.

Classical cadherins are the best studied group and include epithelial E-cadherin (CDH1), neuronal N-cadherin (CDH2), and placental P-cadherin (CDH3), among others. Vascular endothelial (VE-) cadherin (CDH5) is important for endothelial junctions. In addition to classical cadherins, the cadherin superfamily also includes desmosomal cadherins, such as desmogleins and desmocollins, which contribute to strong cell–cell adhesion in tissues subjected to mechanical stress. Protocadherins and other related cadherin-related proteins are abundant in the nervous system and are implicated in cellular recognition and connectivity.

Molecularly, the extracellular domain consists of multiple EC repeats, with calcium ions stabilizing the rigid structure that supports adhesion. The intracellular domain binds catenins (such as β-catenin, α-catenin, and p120-catenin), linking cadherin-mediated junctions to the actin cytoskeleton and participating in intracellular signaling. Cadherins influence tissue architecture, polarity, and morphogenesis, and can modulate signaling pathways, including Wnt/β-catenin, through β-catenin availability.

Dysregulation of cadherins is associated with developmental disorders and diseases, notably cancer, where loss of E-cadherin function can promote epithelial–mesenchymal transition and metastasis.