Details

Autor(en) / Beteiligte

• Oakley, Robert H.
• Laporte, Stéphane A.
• Holt, Jason A.
• Caron, Marc G.
• Barak, Larry S.

Titel

Differential Affinities of Visual Arrestin, βArrestin1, and βArrestin2 for G Protein-coupled Receptors Delineate Two Major Classes of Receptors

Ist Teil von

• The Journal of biological chemistry, 2000-06, Vol.275 (22), p.17201-17210

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2000

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.