GRK1167 TP10 The role of the ADAP/SKAP55/RIAM module for CXCR4-mediated adhesion and migration of T cells

In T lymphocytes, the most important cells of the adaptive immune system, the cytolsolic adapter protein ADAP (Adhesion and Degranulaton-promoting Adaptor Protein) is constitutive associated with yet two other cytosolic adaptor proteins SKAP55 (Src Kinase-associated Phosphoprotein of 55 kDa) and RIAM (Rap1-Interacting Adaptor Molecule). We have recently shown that the ADAP/SKAP55/RIAM module regulates TCR-mediated activation of 1- and 2-integrins by facilitating plasma membrane targeting of the GTPase Rap1, which binds in its activated GTP-loaded form to the RA-domain of RIAM. TCR-mediated activation of 1- and 2-integrins (also called inside-out-signaling) is a very important process e.g. for the stable interaction of T cells with antigen-presenting cells at the onset of an immune response. In addition, chemokine-mediated adhesion of T lymphocytes, is also crucial for the interaction with endothelial cells and the subsequent chemotaxis to secondary lymphatic organs (T cell homing). Our preliminary work indicates that the ADAP/SKAP55/RIAM module is also involved in CXCR4-mediated migration. In the present study, we want to examine the role of the ADAP/SKAP55/RIAM module for CXCR4-mediated T cell adhesion, polarization, and migration.