Figure 6. Class B CCR5 trafficking pathway triggered by CCR5 Ab Pos in T cells.

Upon stimulation with CCR5 Ab Pos, the CCR5 receptor associates with G protein and G protein-coupled receptor kinases (GRKs) induce receptor phosphorylation. β-arrestin1/2 can initiate desensitization, thus contributing to the internalization of CCR5 by clathrin-coated pits. In particular, β-arrestin2 accumulates in protein complexes with activated CCR5 and leads to activation and retention in the cytoplasm of MAP kinase ERK1. These events contribute to the formation of a CCR5 signalosome with β-arrestin2 and ERK1 into the cytosol, which remains stable from 150′ up to 48 h. The signalosome could be targeted for degradation with consequent de novo synthesis of the proteins complex (CCR5, β-arrestin2, ERK1). As a consequence, CCR5 reappears on the cell surface with long lasting kinetics (8 days).