Exp Mol Med.  2006 Jun;38(3):191-195.

The role of the alpha4 integrin-paxillin interaction in regulating leukocyte trafficking

Affiliations
  • 1Department of Medicine, University of California/VA Medical Center, San Diego, CA, USA. drose@vapop.ucsd.edu

Abstract

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 alpha 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.

Keyword

alpha4 integrins; autoimmune diseases; leukocyte trafficking; paxillin

MeSH Terms

Protein Binding
Paxillin/*metabolism/physiology
Models, Biological
Leukocytes/cytology/*metabolism
Integrin alpha4beta1/metabolism/physiology
Integrin alpha4/*metabolism/physiology
Humans
Cell Movement/*physiology
Cell Adhesion/physiology
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