Roles of cell adhesion molecules nectin and nectin-like molecule-5 in the regulation of cell movement and proliferation

In response to chemoattractants, migrating cells form protrusions, such as lamellipodia and filopodia, and structures, such as ruffles over lamellipodia, focal complexes and focal adhesions at leading edges. The formation of these leading edge structures is essential for directional cell movement. Nectin-like molecule-5 (Necl-5) interacts in cis with PDGF receptor and integrin alpha(v)beta(3), and enhances the activation of signalling molecules associated with these transmembrane proteins, which results in the formation of leading edge structures and enhancement of directional cell movement. When migrating cells come into contact with each other, cell-cell adhesion is initiated, resulting in reduced cell velocity. Necl-5 first interacts in trans with nectin-3. This interaction is transient and induces down-regulation of Necl-5 expression at the cell surface, resulting in reduced cell movement. Cell proliferation is also suppressed by the down-regulation of Necl-5, because the inhibitory effect of Necl-5 on Sprouty2, a negative regulator of the Ras signalling, is diminished. PDGF receptor and integrin alpha(v)beta(3), which have interacted with Necl-5, then form a complex with nectin, which initiates cell-cell adhesion and recruits cadherin to the nectin-based cell-cell adhesion sites to form stable adherens junctions. The formation of adherens junctions stops cell movement, in part through inactivation of integrin alpha(v)beta(3) caused by the trans-interaction of nectin. Thus, nectin and Necl-5 play key roles in the regulation of cell movement and proliferation.