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Cell migration

Regulating 'stickiness': a key role for RAPL

Nature Reviews Immunology volume 4, page 752 (2004)Cite this article

Recently, these researchers identified RAPL as an effector molecule for the GTPase RAP1, which is known to activate integrins, such as lymphocyte function-associated antigen 1 (LFA1) and very late antigen 4 (VLA4), and invoke cell polarization and motility. So, to investigate whether RAPL is important in immune-cell trafficking in vivo, they generated RAPL-deficient mice. T and B cells isolated from these mice had reduced ability to adhere to ICAM1 or VCAM1 (the ligands for LFA1 and VLA4, respectively) when exposed to chemokines, even though expression levels of the integrins or chemokine receptors were indistinguishable from those of wild-type cells. In addition, in the presence of chemokines, the RAPL-deficient lymphocytes had impaired adhesion and transmigration through endothelial-cell monolayers. In wild-type cells, chemokine-stimulated LFA1 activation by RAP1 is accompanied by lymphocyte polarization; however, the authors did not see a redistribution of LFA1 in the RAPL-deficient cells following chemokine stimulation, indicating a crucial role for RAPL in integrin activation.

Owing to these functional defects in lymphocyte adhesion and migration, RAPL-deficient mice had reduced T- and B-cell numbers in the spleen and lymph-node follicles, indicating impaired homing to peripheral lymphoid organs. Similarly, in the absence of RAPL, CD11c+ splenic dendritic cells (DCs) and epidermal Langerhans cells showed markedly reduced migration to the white pulp of the spleen or draining lymph nodes after exposure to an inflammatory stimulus.

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References

ORIGINAL RESEARCH PAPER

  1. Katagiri, K. et al. Crucial functions of the RAP1 effector molecule RAPL in lymphocyte and dendritic cell trafficking. Nature Immunol. 7 September 2004 (doi:10.1038/ni1111).

FURTHER READING

  1. Price, L. S. & Bos, J. L. RAPL: taking the Rap in immunity. Nature Immunol. 5, 1007–1008 (2004).

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Authors
  1. Lucy Bird
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Bird, L. Regulating 'stickiness': a key role for RAPL. Nat Rev Immunol 4, 752 (2004). https://doi.org/10.1038/nri1475

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