Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor

Nature. 1996 Oct 3;383(6599):447-50. doi: 10.1038/383447a0.


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 beta2-adrenergic receptor (beta2AR). beta2AR signalling is rapidly attenuated through receptor phosphorylation and subsequent binding of the protein beta-arrestin. Ultimately the receptor undergoes internalization, and although the molecular mechanism is unclear, receptor phosphorylation and beta-arrestin binding have been implicated in this processs. Here we report that beta-arrestin and arrestin-3, but not visual arrestin, promote beta2AR internalization and bind with high affinity directly and stoichiometrically to clathrin, the major structural protein of coated pits. Moreover, beta-arrestin/arrestin chimaeras that are defective in either beta2AR or clathrin binding show a reduced ability to promote beta2AR endocytosis. Immunofluorescence microscopy of intact cells indicates an agonist-dependent colocalization of the beta2AR and beta-arrestin with clathrin. These results show that beta-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arrestins / genetics
  • Arrestins / metabolism*
  • COS Cells
  • Cattle
  • Cell Line
  • Clathrin / metabolism*
  • Endocytosis / physiology*
  • GTP-Binding Proteins / metabolism
  • Protein Binding
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • beta-Arrestins


  • Arrestins
  • Clathrin
  • Receptors, Adrenergic, beta-2
  • Recombinant Fusion Proteins
  • arrestin3
  • beta-Arrestins
  • GTP-Binding Proteins