Cooperative Roles of Nectins with Cadherins in Physiological and Pathological Processes

Mammalian tissues and organs are composed of cells of different types and these cells adhere to one another to form societies of cells including the mesenchyme and the epithelium. Cell–cell adhesion in the mesenchyme is weak whereas cells are organized into closely adherent barrier-forming sheets by cell–cell adhesions in the epithelium. Cell–cell adhesion is organized to allow the release or incorporation of individual cells during various physiological or pathological processes, for example, organ development and growth, maintenance and repair of tissues, or tumorigenesis. One prominent cell–cell adhesion apparatus is adherens junctions (AJs). The central structural components of AJs are transmembrane cell–cell adhesion molecules, cadherins and nectins. Nectins recruit cadherins to the cell–cell contact sites and mediate cell–cell adhesions that control local membrane dynamics for cell polarization and coordinate shape change at the cellular level. Nectins are engaged in calcium-independent homophilic and heterophilic trans-interactions between opposing cells in numerous tissues and cell types to form homotypic and heterotypic cell–cell adhesion, whereas cadherins are primarily involved in calcium-dependent homophilic trans-interactions between opposing cells to form homotypic cell–cell adhesion. Nectins function cooperatively with or independently of cadherins to control physiological processes and cooperative ones include the formation of AJs and apico-basal polarity, apical constriction, contact inhibition of cell movement and proliferation, formation of synapse, formation of checkerboard-like cell arrangement, ciliary epithelium and lens, and neuronal cell adhesion and migration. Moreover, nectins are involved in pathological processes including virus infection and human inherited disorder.