Differential Affinities of Visual Arrestin, βArrestin1, and βArrestin2 for G Protein-coupled Receptors Delineate Two Major Classes of Receptors*
By R. Oakley, S. Laporte, J. Holt, M. Caron, L. Barak. Journal of Biological Chemistry, 2000
663 citations recorded by the source corpus.
Visual arrestin, βarrestin1, and βarrestin2 comprise a family of intracellular proteins that desensitize G protein-coupled receptors (GPCRs). In addition, βarrestin1 and βarrestin2 target desensitized receptors to clathrin-coated pits for endocytosis. Whether arrestins differ in their ability to interact with GPCRs in cells is not known. In this study, we visualize the interaction of arrestin family members with GPCRs in real time and in live cells using green fluorescent protein-tagged arrestins. In the absence of agonist, visual arrestin and βarrestin1 were found in both the cytoplasm and nucleus of HEK-293 cells, whereas βarrestin2 was found only in the cytoplasm. Analysis of agonist-mediated arrestin translocation to multiple GPCRs identified two major classes of receptors. Class A receptors (β2 adrenergic receptor, mu opioid receptor, endothelin type A receptor, dopamine D1A receptor, and α1b adrenergic receptor) bound βarrestin2 with higher affinity than βarrestin1 and did not interact with visual arrestin. In contrast, class B receptors (angiotensin II type 1A receptor, neurotensin receptor 1, vasopressin V2 receptor, thyrotropin-releasing hormone receptor, and substance P receptor) bound both βarrestin isoforms with similar high affinities and also interacted with visual arrestin. Switching the carboxyl-terminal tails of class A and class B receptors completely reversed the affinity of each receptor for the visual and non-visual arrestins. In addition, exchanging the βarrestin1 and βarrestin2 carboxyl termini reversed their extent of binding to class A receptors as well as their subcellular distribution. These results reveal for the first time marked differences in the ability of arrestin family members to bind GPCRs at the plasma membrane. Moreover, they show that visual arrestin can interact in cells with GPCRs other than rhodopsin. These findings suggest that GPCR signaling may be differentially regulated depending on the cellular complement of arrestin isoforms and the ability of arrestins to interact with other cellular proteins.
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Citations in the corpus
- Molecular Mechanism of β-Arrestin-Biased Agonism at Seven-Transmembrane Receptors (2011, result): “This idea is consistent with previous results showing that the presence or absence of serine and threonine clusters in the receptor C terminus regulates the affinity of β-arrestin recruitment and the pattern of intracellular trafficking for a large number of 7TMRs (76, 77).”
- GRKs and β-arrestins: roles in receptor silencing, trafficking and signaling (2006, background): “A conserved Ser‐Thr cluster in the carboxy-terminal tail of certain 7TMRs appears to condition the strength of receptor‐b-arrestin interaction, and its presence or absence can be used to define two classes of 7TMRs [19, 20 ].”
- Desensitization of G protein-coupled receptors and neuronal functions. (2004, background): “In these in vitro studies, analysis of agonist-mediated arrestin translocation to multiple GPCRs identified two major classes of receptors (Class A and Class B), which differ in relative affinity for βarrestin-1 versus βarrestin-2 and in internalization/recycling properties (Oakley et al. 2000).”
- The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. (2002, methodology): “Using this approach, Oakley et al. have recently shown that GPCRs exhibit different patterns of agonist-induced β-arrestin interaction, which allow the receptors to be grouped into two distinct classes (Oakley et al., 2000) (Fig.”
- Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. (2001, unknown): “sidered to play a predominant role in the endocytosis of most GPCRs (Oakley et al., 2000; Santini et al., 2000).”