The role of the α4 integrin-paxillin interaction in regulating leukocyte trafficking

The movement of leukocytes from the blood into peripheral tissues is a central feature of immune surveillance, but also contributes to the pathogenesis of inflammatory and autoimmune diseases. Integrins are a family of adhesion and signaling molecules made up of paired a and P subunits, and the integrin alpha 4 beta 1 plays a prominent role in the trafficking of mononuclear leukocytes. We have previously described the direct interaction of the signaling adaptor molecule paxillin with the cytoplasmic domain of the alpha 4 integrin subunit. This interaction is critical for alpha 4 beta 1 integrin dependent cell adhesion under shear flow conditions as it provides a needed connection to the actin cytoskeleton. Furthermore, the alpha 4-paxillin interaction is required for effective alpha 4 beta 1 dependent leukocyte migration and does so through the temporal and spatial regulation of the small GTPase Rac. These findings make the alpha 4-paxillin interaction a potentially attractive therapeutic target in controlling leukocyte trafficking.