Regulation of adhesion site dynamics by integrin traffic

The dynamic control of integrin-mediated cell adhesion to extracellular matrix proteins is crucial for several physiological and pathological phenomena as diverse as embryonic morphogenesis, muscle contraction, tissue repair, and cancer cell dissemination. On one hand, the intrinsic conformational plasticity of integrins, which can be bidirectionally modulated by their ligands and cytosolic adaptors in combination with physical forces, is a key regulatory parameter. On the other hand, endo-exocytic integrin traffic logistics represent an additional important mode of control. Herein, we highlight how these two apparently parallel and independent strategies for tuning integrin function appear instead to be indissolubly intermingled, as eukaryotic cells have evolved distinct molecular strategies and endosomal pathways to traffic ligand-bound and ligand-free integrins.