Role of Phosphorylation in the Control of Clathrin-Mediated Internalization of GPCR

Figure 1

Steps conducting to G protein coupled receptors internalization. Internalization and recycling of GPCRs. Upon agonist binding, receptors are phosphorylated (P) by GRKs leading to the recruitment of β-arrestins (step 1). Beta-arrestins, through their interaction with clathrin and AP-2, target the receptor/arrestin complexes to clathrin coated pits (step 2). Beta-arrestins also bind c-Src (steps 2 and 3). Dynamin (step 3), a GTPase, regulates the pinching off from the cell surface of clathrin-coated pits (steps 3 and 4). Once clathrin-coated vesicles are formed (step 4), the receptor is then internalized into endosomes (step 5), dephosphorylated before returning to the cell surface (step 6), or the receptor is degradated to lysosomes (step 7).