SLAT promotes TCR-mediated, Rap1-dependent LFA-1 activation and adhesion through interaction of its PH domain with Rap1
| Autor: | Marjorie Côte, Stéphane Bécart, Camille Fos, Ann J. Canonigo-Balancio, Klaus Ley, Amnon Altman |
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| Rok vydání: | 2015 |
| Předmět: |
T cell
Immunology Integrin Receptors Antigen T-Cell Mice Transgenic Cell Line Immunological synapse Mice Cell Adhesion medicine Immunology and Allergy Animals Guanine Nucleotide Exchange Factors Lymphocyte function-associated antigen 1 Cell adhesion biology T-cell receptor Nuclear Proteins rap1 GTP-Binding Proteins Cell Biology Lymphocyte Function-Associated Antigen-1 Protein Structure Tertiary Cell biology DNA-Binding Proteins rap GTP-Binding Proteins medicine.anatomical_structure biology.protein Rap1 Signal transduction Signal Transduction Research Article |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.172742 |
| Popis: | SLAT (also known as DEF6) promotes T cell activation and differentiation by regulating NFAT-Ca2+ signaling. However, its role in TCR-mediated inside-out signaling, which induces integrin activation and T cell adhesion, a central process in T cell immunity and inflammation, has not been explored. Here, we show that SLAT is crucial for TCR-induced adhesion to ICAM-1 and LFA-1 affinity maturation in CD4+ T cells. Mechanistic studies revealed that SLAT interacts, through its PH domain, with a key component of inside-out signaling, namely the active form of the small GTPase Rap1. This interaction has been further shown to facilitate the interdependent recruitment of Rap1 and SLAT to the T cell immunological synapse upon TCR engagement. Furthermore, a SLAT mutant lacking its PH domain drastically inhibited LFA-1 activation and CD4+ T cell adhesion. Finally, we established that a constitutively active form of Rap1, which is present at the plasma membrane, rescues the defective LFA-1 activation and ICAM-1 adhesion in SLAT-deficient (Def6−/−) T cells. These findings ascribe a new function to SLAT, and identify Rap1 as a target of SLAT function in TCR-mediated inside-out signaling. |
| Databáze: | OpenAIRE |
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