cadherines

Cadherins are a family of calcium-dependent transmembrane proteins that mediate cell–cell adhesion in animals. They function at adherens junctions to help maintain tissue architecture, regulate cell sorting during development, and participate in signaling processes. Classical cadherins such as E-cadherin, N-cadherin, and P-cadherin are the best studied, while non-classical cadherins include desmosomal cadherins (desmogleins and desmocollins) and protocadherins, which contribute to cell–cell contacts in various tissues.

Classical cadherins share a common architecture: an extracellular region composed of five cadherin repeats (EC domains) that mediate homophilic adhesion, a single-pass transmembrane segment, and a cytoplasmic tail. Calcium ions bind between EC repeats, stabilizing the rigid extracellular domain and enabling specific, calcium-dependent binding to cadherins on neighboring cells. Adhesion is strengthened by clustering at junctions and by connections to the actin cytoskeleton through a set of linker proteins, including catenins (alpha-, beta-, and gamma-catenin) and regulatory proteins such as p120-catenin.

Functionally, cadherins govern cell sorting and tissue boundary formation during embryonic development, contribute to the maintenance of epithelial and endothelial barriers, and participate in mechanochemical signaling. Beta-catenin can link cadherins to Wnt signaling under certain conditions, linking adhesion to transcriptional regulation.

Clinical and biological significance: loss or mutation of cadherins, particularly E-cadherin (CDH1), is associated with cancer progression and metastasis due to weakened cell adhesion. E-cadherin dysfunction is linked to hereditary diffuse gastric cancer and lobular breast cancer. VE-cadherin maintains vascular integrity, and tissue-specific cadherins contribute to organ development and homeostasis.

Diversity and evolution: Cadherins comprise a large gene superfamily found across metazoans, including classical, desmosomal, and protocadherins, reflecting diverse roles in tissue specificity and signaling.