Regulation of immune cell adhesion and migration by regulator of adhesion and cell polarization enriched in lymphoid tissues.

Rap1 has emerged as an important regulator of adhesion in multicellular organisms. In the immune system, Rap1 functions as an inside-out signalling molecule for leucocyte integrins following stimulation with chemokines or antigens. Regulator of adhesion and cell polarization enriched in lymphoid tissues (RAPL) is a novel Rap1 effector molecule that mediates Rap1 signalling to integrins. The Rap1-RAPL complex regulates the spatial distribution of the integrin lymphocyte function-associated antigen-1 as well as cell polarization. The linking of inside-out signalling with polarization synergistically promotes highly efficient lymphocyte trafficking. Targeted deletion of RAPL in mice has demonstrated multiple indispensable roles for this protein in lymphocyte and dendritic cell trafficking critical for immunosurveillance.