Role of endocytosis in mediating downregulation of G-protein-coupled receptors

Many G-protein-coupled receptors (GPCRs) undergo agonist-induced endocytosi s. Such endocytosis has been implicated in diverse processes of receptor re gulation, including reversible sequestration of receptors in endosomes and proteolytic downregulation of receptors in lysosomes. The precise relations hips between membrane pathways that mediate receptor sequestration and down regulation remain controversial. Recent studies suggest that GPCRs can be s egregated within distinct microdomains of the plasma membrane before endocy tosis occurs, and others suggest that certain GPCRs are sorted between dive rgent membrane pathways after endocytosis by clathrin-coated pits. Furtherm ore, emerging data implicate a specific role of the actin cytoskeleton and receptor phosphorylation in controlling endocytic sorting of a particular G PCR. In this article, recent research into endocytosis of GPCRs will be dis cussed together with some important and unresolved questions regarding the diversity and specificity of mechanisms that mediate downregulation of GPCR s.