The Interaction of β-Arrestin with the AP-2 Adaptor Is Required for the Clustering of β2-Adrenergic Receptor into Clathrin-coated Pits*
By S. Laporte, R. Oakley, J. Holt, L. Barak, M. Caron. Journal of Biological Chemistry, 2000
306 citations recorded by the source corpus.
β-Arrestins are cytosolic proteins that regulate the signaling and the internalization of G protein-coupled receptors (GPCRs). Although termination of receptor coupling requires β-arrestin binding to agonist-activated receptors, GPCR endocytosis involves the coordinate interactions between receptor-β-arrestin complexes and other endocytic proteins such as adaptor protein 2 (AP-2) and clathrin. Clathrin interacts with a conserved motif in the β-arrestin C-terminal tail; however, the specific molecular determinants in β-arrestin that bind AP-2 have not been identified. Moreover, the respective contributions of the interactions of β-arrestin with AP-2 and clathrin toward the targeting of GPCRs to clathrin-coated vesicles have not been established. Here, we identify specific arginine residues (Arg394 and Arg396) in the β-arrestin 2 C terminus that mediate β-arrestin binding to AP-2 and show, in vitro, that these domains in β-arrestin 1 and 2 interact equally well with AP-2 independently of clathrin binding. We demonstrate in HEK 293 cells by fluorescence microscopy that β2-adrenergic receptor-β-arrestin complexes lacking the β-arrestin-clathrin binding motif are still targeted to clathrin-coated pits. In marked contrast, receptor-β-arrestin complexes lacking the β-arrestin/AP-2 interactions are not effectively compartmentalized in punctated areas of the plasma membrane. These results reveal that the binding of a receptor-β-arrestin complex to AP-2, not to clathrin, is necessary for the initial targeting of β2-adrenergic receptor to clathrin-coated pits.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Spectroscopy
View Paper: https://www.semanticscholar.org/paper/7d76fd4b4fd77f5c1c2c46e461e77f59e2fe0ac5
Citations in the corpus
- Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. (2001, unknown): “Moreover, whereas  2 AR/-arrestin complexes lacking the -arrestin clathrin binding motif redistributed to coated pits, receptor/-arrestin complexes lacking the 2-adaptin binding site did not (Laporte et al., 2000).”