Nectin-3

Nectin-3 (PVRL3, nectin-3/CD113) is the third member of the nectin subfamily of Ig-like cell adhesion molecules, existing as at least three splice isoforms with distinct cytoplasmic and transmembrane regions. Nectin-3 mediates calcium-independent cell-cell adhesion through strong heterophilic trans-interactions with nectin-1 and nectin-2, and homophilic self-binding, nucleating adherens junctions in cooperation with afadin and cadherins at epithelial and endothelial contacts. Its best-characterized physiological roles are developmental: nectin-1/nectin-3 and nectin-2/nectin-3 pairs organize the specialization of Sertoli cell-spermatid junctions in the testis (PVRL3 mutations cause male infertility with sperm-head deformity), cone and rod photoreceptor synapse patterning in the retina, hair follicle development and neuronal migration. In the immune system, nectin-3 serves as a ligand for inhibitory receptors on NK cells and T cells, engaging TIGIT more strongly than DNAM-1 in certain contexts, thereby participating in checkpoint signaling, and it is expressed on dendritic cells where it influences immune synapse formation and antigen presentation.