RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1.
The small GTPase Rap1 is a potent activator of leukocyte integrin. However, the regulatory mechanism involved is unknown. Here, we identify the Rap1 effector, RAPL, as an essential regulator in this activation. RAPL was enriched in mouse lymphoid tissues and associated with Rap1 after stimulation by the T cell receptor and with chemokine CXCL12. Human RAPL stimulated lymphocyte polarization and the patch-like redistribution of lymphocyte-function-associated antigen 1 (LFA-1) to the leading edge, resulting in enhanced adhesion to intercellular adhesion molecule 1 (ICAM-1). Triggered by activated Rap1, RAPL associated with LFA-1 and rapidly relocated to the leading edge and accumulated at immunological synapses. Thus, RAPL regulates lymphocyte adhesion through the spatial distribution of LFA-1.
Katagiri
Koko
K
Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida-konoe, Sakyo-ku, Kyoto 606-8501 Japan.
Maeda
Akito
A
Shimonaka
Mika
M
Kinashi
Tatsuo
T
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002448:Cell Adhesion / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D020559:Monomeric GTP-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D020827:rap1 GTP-Binding Proteins; C454042:RASSF5 protein, human; C455831:Rassf5 protein, mouse