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        Analysis of Chemokine Receptor Endocytosis and Recycling

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        Endocytosis regulates the cell-surface expression of many seven transmembrane G-protein coupled receptors (7 TM-GPCRs) and has been implicated in both desensitization following agonist-induced activation and resensitization (1 ,2 ). The internalization mechanism for many 7 TM-GPCRs has not been clearly established. However, a clear paradigm is emerging for the β2 -adrenergic receptor (β2 AR) (1 ,2 ). For β2 AR, agonist binding induces activation of heterotrimeric G proteins, which in turn activate one or more members of the family of G-protein coupled receptor kinases (GRKs). GRK-mediated phosphorylation of the receptor enhances the binding of β-arrestins, proteins that uncouple heterotrimeric G protein activation and link the receptor to clathrincoated pits by binding to clathrin heavy chains (1 3 ). Coated vesicles internalize the receptors and deliver them to endosomes, where they can be dephosphorylated and recycled to the cell surface (4 ).
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