FIGURE 6.

Desensitization and trafficking of GPCRs. Upon ligand binding, GPCRs traditionally signal via G proteins (1). In addition, GPCRs are phosphorylated on S and T residues in their C-terminus or ICLs by GRKs (2). β-arrestins bind to phosphorylated GPCRs and prevent further coupling of G proteins, a process known as desensitization (3). β-arrestins target phosphorylated GPCRs for endocytosis via clathrin-coated pits (CCPs) by scaffolding proteins of the internalization-machinery (4). Internalized receptors may activate β-arrestin-dependent signaling (5). Internalized GPCRs are subsequently sorted to recycling endosomes (6) or to lysosomes for degradation (7).