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RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1

Nature Immunology volume 4, pages 741–748 (2003)Cite this article

Abstract

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.

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Figure 1: RAPL amino acid sequence, tissue distribution and association with Rap1.
Figure 2: RAPL mediates adhesion by LFA-1 and ICAM-1.
Figure 3: Polarized LFA-1 redistribution.
Figure 4: Distribution of RAPL and LFA-1.
Figure 5: RAPL in immunological synapse.

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Acknowledgements

This work was supported in part by a grant-in aid from the Ministry of Education, Science, Sports, and Culture of Japan, and the Cell Science Research Foundation.

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Authors and Affiliations

  1. Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida-konoe, Sakyo-ku, Kyoto, 606-8501, Japan

    Koko Katagiri, Akito Maeda, Mika Shimonaka & Tatsuo Kinashi

  2. Department of Dermatology, Graduate School of Medicine, Kyoto University, Yoshida-konoe, Sakyo-ku, Kyoto, 606-8501, Japan

    Mika Shimonaka

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Correspondence to Tatsuo Kinashi.

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Katagiri, K., Maeda, A., Shimonaka, M. et al. RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nat Immunol 4, 741–748 (2003). https://doi.org/10.1038/ni950

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