Figure 7. A schematic summary of the regulation of agonist-induced β₂-AR trafficking by S-nitrosylation/denitrosylation of β-arrestin 2, GRK2 and dynamin.

(A) β-arrestin 2 (β-Arr 2) serves as a scaffold to functionally co-localize eNOS and β-ARs (as well as other G-protein-coupled receptors, GPCRs). Ligand (isoproterenol) stimulation results in activation of eNOS and S-nitrosylation of β-arrestin 2. S-nitrosylation of β-arrestin 2 promotes its dissociation from eNOS and association with clathrin HC/β-adaptin, which facilitates routing of the β₂-AR into the clathrin-based endocytotic pathway, and β-arrestin 2 is subsequently denitrosylated. (B) Ligand-coupled inhibition of GPCR kinase 2 (GRK2) by S-nitrosylation suppresses agonist-stimulated β-AR phosphorylation, β-arrestin recruitment, and receptor desensitization and down-regulation. (C) Following GPCR activation, eNOS-mediated S-nitrosylation of dynamin promotes multimerization and GTPase activity, which facilitates scission of endocytotic vesicles and receptor internalization.