Integrin regulation of lymphocyte trafficking: lessons from structural and signaling studies.
High trafficking capability of lymphocytes is crucial in immune surveillance and antigen responses. Central to this regulatory process is a dynamic control of lymphocyte adhesion behavior regulated by chemokines and adhesion receptors such as integrins. Modulation of lymphocyte adhesive responses occurs in a wide range of time window from less than a second to hours, enabling rolling lymphocyte to attach to and migrate through endothelium and interact with antigen-presenting cells. While there has been a rapid progress in the understanding of integrin structure, elucidation of signaling events to relay extracellular signaling to integrins in physiological contexts has recently emerged from studies using gene-targeting and gene-silencing technique. Regulatory molecules critical for integrin activity control distribution of integrins, polarized cell morphology and motility, suggesting a signaling network that coordinates integrin function with lymphocyte migration. Here, I review recent studies of integrin structural changes and intracellular signal molecules that trigger integrin activation (inside-out signals), and discuss molecular mechanisms that control lymphocyte integrins and how inside-out signals coordinately modulate adhesive reactions and cell shape and migration.
Kinashi
Tatsuo
T
Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Kyoto 606, Japan.
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D016023:Integrins