Noncanonical functions of adhesion proteins in inflammation.

Cell adhesion proteins localize to epithelial and endothelial cell membranes to form junctional complexes between neighboring cells or between cells and the underlying basement membrane. The structural and functional integrities of these junctions are critical to establish cell polarity and maintain tissue barrier function, while also facilitating leukocyte migration and adhesion to sites of inflammation. In addition to their adhesive properties, however, junctional proteins can also serve important noncanonical functions in inflammatory signaling and transcriptional regulation. Intriguingly, recent work has unveiled novel roles for cell adhesion proteins as both signaling initiators and downstream targets during inflammation. In this review, we discuss both the traditional functions of junction proteins in cell adhesion and tissue barrier function as well as their noncanonical signaling roles that have been implicated in facilitating diverse inflammatory pathologies.