Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking
- PMID: 15361866
- DOI: 10.1038/ni1111
Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking
Abstract
Immunosurveillance requires the coordinated regulation of chemokines and adhesion molecules to guide immune cell migration. However, the critical molecule for governing the high trafficking capability of immune cells is not clear. Here we show that the effector molecule RAPL is indispensable in the integrin-mediated adhesion and migration of lymphocytes and dendritic cells. RAPL deficiency caused defective chemokine-triggered lymphocyte adhesion and migration to secondary lymphoid organs, resulting in atrophic lymphoid follicles and deficient marginal zone B cells, concomitant with increased immature B cells in the blood. Furthermore, splenic dendritic cells were diminished and defective in adhesion. After being activated with inflammatory stimuli, skin and splenic dendritic cells failed to migrate into either the draining lymph nodes or the white pulp of the spleen. Thus, RAPL is a crucial immune cell trafficking regulator essential for immunosurveillance.
Comment in
-
RAPL: taking the Rap in immunity.Nat Immunol. 2004 Oct;5(10):1007-8. doi: 10.1038/ni1004-1007. Nat Immunol. 2004. PMID: 15454926 No abstract available.
Similar articles
-
Regulation of lymphocyte adhesion and migration by the small GTPase Rap1 and its effector molecule, RAPL.Immunol Lett. 2004 Apr 30;93(1):1-5. doi: 10.1016/j.imlet.2004.02.008. Immunol Lett. 2004. PMID: 15134891 Review.
-
Regulation of immune cell adhesion and migration by regulator of adhesion and cell polarization enriched in lymphoid tissues.Immunology. 2005 Oct;116(2):164-71. doi: 10.1111/j.1365-2567.2005.02214.x. Immunology. 2005. PMID: 16162265 Free PMC article. Review.
-
RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1.Nat Immunol. 2003 Aug;4(8):741-8. doi: 10.1038/ni950. Epub 2003 Jul 6. Nat Immunol. 2003. PMID: 12845325
-
Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion.Nat Immunol. 2006 Sep;7(9):919-28. doi: 10.1038/ni1374. Epub 2006 Aug 6. Nat Immunol. 2006. PMID: 16892067
-
Role of chemokines in trafficking of lymphocytes and dendritic cells.Int J Hematol. 2000 Dec;72(4):399-407. Int J Hematol. 2000. PMID: 11197204 Review.
Cited by
-
Nore1B regulates TCR signaling via Ras and Carma1.Cell Signal. 2006 Oct;18(10):1647-54. doi: 10.1016/j.cellsig.2006.01.015. Epub 2006 Mar 7. Cell Signal. 2006. PMID: 16520020 Free PMC article.
-
Structural basis of inactivation of Ras and Rap1 small GTPases by Ras/Rap1-specific endopeptidase from the sepsis-causing pathogen Vibrio vulnificus.J Biol Chem. 2018 Nov 23;293(47):18110-18122. doi: 10.1074/jbc.RA118.004857. Epub 2018 Oct 3. J Biol Chem. 2018. PMID: 30282804 Free PMC article.
-
Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors.Blood. 2009 Sep 24;114(13):2657-66. doi: 10.1182/blood-2009-01-201632. Epub 2009 Jul 23. Blood. 2009. PMID: 19628705 Free PMC article.
-
The ins and outs of leukocyte integrin signaling.Annu Rev Immunol. 2009;27:339-62. doi: 10.1146/annurev.immunol.021908.132554. Annu Rev Immunol. 2009. PMID: 19302044 Free PMC article. Review.
-
Rap1b regulates B cell development, homing, and T cell-dependent humoral immunity.J Immunol. 2008 Sep 1;181(5):3373-83. doi: 10.4049/jimmunol.181.5.3373. J Immunol. 2008. PMID: 18714009 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases