Role of endocytosis in mediating downregulation of G-protein-coupled receptors.
Many G-protein-coupled receptors (GPCRs) undergo agonist-induced endocytosis. Such endocytosis has been implicated in diverse processes of receptor regulation, including reversible sequestration of receptors in endosomes and proteolytic downregulation of receptors in lysosomes. The precise relationships between membrane pathways that mediate receptor sequestration and downregulation remain controversial. Recent studies suggest that GPCRs can be segregated within distinct microdomains of the plasma membrane before endocytosis occurs, and others suggest that certain GPCRs are sorted between divergent membrane pathways after endocytosis by clathrin-coated pits. Furthermore, emerging data implicate a specific role of the actin cytoskeleton and receptor phosphorylation in controlling endocytic sorting of a particular GPCR. In this article, recent research into endocytosis of GPCRs will be discussed together with some important and unresolved questions regarding the diversity and specificity of mechanisms that mediate downregulation of GPCRs.
Tsao
P
P
Dept of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0984, USA.
Cao
T
T
von Zastrow
M
M
D000818:Animals; D015536:Down-Regulation / Q000235:genetics* / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D006801:Humans; D015398:Signal Transduction / Q000235:genetics
D019204:GTP-Binding Proteins