Regulation of lymphocyte adhesion and migration by the small GTPase Rap1 and its effector molecule, RAPL.
Dynamic regulation of integrin-mediated adhesion is central to lymphocyte trafficking and antigen recognition. The small GTPase Rap1 is a potent stimulator of leukocyte integrins through modulation of affinity and avidity. In addition, lymphocyte Rap1 has unique abilities to trigger cell polarization and enhance cell motility. These characteristics of Rap1 contribute to adhesive interactions with antigen-presenting cells (APC) and the vascular endothelium. In the process of elucidating the molecular mechanisms of Rap1-mediated integrin activation, we have identified a novel Rap1-binding molecule, regulator of adhesion and cell polarization enriched in lymphoid tissues (RAPL). RAPL is predominantly expressed in immune cells, and mediates Rap1-triggered integrin activation upon TCR engagement and chemokine stimulation. Importantly, Rap1/RAPL signaling cooperatively regulates cell polarization and integrin activation. The linkage between cell polarization and integrin activation through Rap1/RAPL signaling likely provides immune cells with their dynamic trafficking capability.
Kinashi
Tatsuo
T
Bayer-chair Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University Yoshida-konoe, Sakyo-ku, Kyoto 606-8501, Japan. tkinashi@mfour.med.kyoto-u.ac.jp
Katagiri
Koko
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D018925:Chemokines; D016169:Lymphocyte Function-Associated Antigen-1; D020559:Monomeric GTP-Binding Proteins; D020827:rap1 GTP-Binding Proteins; C454042:RASSF5 protein, human; C455831:Rassf5 protein, mouse