The role of the alpha4 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 beta subunits, and the integrin alpha4beta1 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 alpha4 integrin subunit. This interaction is critical for alpha4beta1 integrin dependent cell adhesion under shear flow conditions as it provides a needed connection to the actin cytoskeleton. Furthermore, the alpha4-paxillin interaction is required for effective alpha4beta1 dependent leukocyte migration and does so through the temporal and spatial regulation of the small GTPase Rac. These findings make the alpha4-paxillin interaction a potentially attractive therapeutic target in controlling leukocyte trafficking.
Rose
David M
DM
Department of Medicine, University of California/VA Medical Center, San Diego, CA, USA. drose@vapop.ucsd.edu
D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D039441:Integrin alpha4 / Q000378:metabolism* / Q000502:physiology; D039041:Integrin alpha4beta1 / Q000378:metabolism / Q000502:physiology; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008954:Models, Biological; D051419:Paxillin / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding
D039041:Integrin alpha4beta1; D051419:Paxillin; D039441:Integrin alpha4