β-Arrestin acts as a clathrin adaptor in endocytosis of the β2-adrenergic receptor (original) (raw)
- Letter
- Published: 03 October 1996
- Jason G. Krupnick1,
- Francesca Santini1,
- Vsevolod V. Gurevich1 nAff2,
- Raymond B. Penn1,
- Alison W. Gagnon1,
- James H. Keen1 &
- …
- Jeffrey L. Benovic1
Nature volume 383, pages 447–450 (1996)Cite this article
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Abstract
THE ability of a system to regulate its responsiveness in the presence of a continuous stimulus, often termed desensitization, has been extensively characterized for the β2-adrenergic receptor (β2AR). β2AR signalling is rapidly attenuated through receptor phosphorylation and subsequent binding of the protein β-arrestin1,2. Ultimately the receptor undergoes internalization3,4, and although the molecular mechanism is unclear, receptor phosphorylation and β-arrestin binding have been implicated in this process5,6. Here we report that p-arrestin and arrestin-3, but not visual arrestin, promote β2AR internalization and bind with high affinity directly and stoichiometrically to clathrin, the major structural protein of coated pits. Moreover, β-arrestin/arrestin chimaeras that are defective in either β2AR or clathrin binding show a reduced ability to promote β2AR endocytosis. Immunofluorescence microscopy of intact cells indicates an agonist-dependent colocalization of the β2AR and β-arrestin with clathrin. These results show that β-arrestin functions as an adaptor in the receptor-mediated endocytosis pathway, and suggest a general mechanism for regulating the trafficking of G-protein-coupled receptors.
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- Vsevolod V. Gurevich
Present address: Sun Health Research Institute, Sun City, Arizona, 85372, USA
Authors and Affiliations
- Department of Biochemistry and Molecular Pharmacology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, USA
Oscar B. Goodman Jr, Jason G. Krupnick, Francesca Santini, Vsevolod V. Gurevich, Raymond B. Penn, Alison W. Gagnon, James H. Keen & Jeffrey L. Benovic
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Goodman, O., Krupnick, J., Santini, F. et al. β-Arrestin acts as a clathrin adaptor in endocytosis of the β2-adrenergic receptor.Nature 383, 447–450 (1996). https://doi.org/10.1038/383447a0
- Received: 27 June 1996
- Accepted: 12 August 1996
- Issue Date: 03 October 1996
- DOI: https://doi.org/10.1038/383447a0