RGD, the Rho’d to cell spreading

Some RGD-type integrins rely on a synergistic site in addition to the canonical RGD site for ligand binding. However, the precise involvement of each of these recognition sites during cell adhesion is still unclear. Here we review recent investigations on integrin αIIbβ3-mediated cell adhesion to immobilized fibrinogen providing evidence that the fibrinogen synergy γ400–411 sequence by itself promotes cell attachment by initiating αIIbβ3 clustering and recruitment of intracellular proteins to focal complexes, while the RGD motif subsequently acts as a molecular switch on the β3 subunit to induce a conformational change necessary for RhoA activation and full cell spreading.