Fig. 1.

Model of the GPCR life cycle. GPCRs are synthesized, folded, and assembled associated with the endoplasmic reticulum (ER). Properly folded receptors are transported from the ER through the Golgi complex to the plasma membrane by passing a quality control process and undergoing post-translational modifications (e.g. glycosylation, methylation, and palmitoylation). Upon agonist stimulation, GPCRs activate their associated G-protein, which in turn dissociates to impact downstream signaling pathways. Prolonged exposure to agonist results in a rapid loss of responsiveness (desensitization) and removal of the receptors from the cell surface (internalization) by phosphorylation (e.g. via GRK) and subsequent arrestin recruitment. Internalized receptors are either targeted to lysosomes for degradation, or recycled back to the cell surface (resensitization).