Clathrin-mediated endocytosis of the beta-adrenergic receptor is regulated by phosphorylation/dephosphorylation of beta-arrestin1.

Published

Journal Article

beta-Arrestins serve a dual regulatory role in the life cycle of G protein-coupled receptors such as the beta2-adrenergic receptor. First, they mediate rapid desensitization by binding to G protein-coupled receptor kinase-phosphorylated receptors. Second, they target the receptors for internalization into endosomal vesicles, wherein receptor dephosphorylation and resensitization occur. Here we report that phosphorylation of a carboxyl-terminal serine (Ser-412) in beta-arrestin1 regulates its endocytotic but not its desensitization function. Cytoplasmic beta-arrestin1 is constitutively phosphorylated and is recruited to the plasma membrane by agonist stimulation of the receptors. At the plasma membrane, beta-arrestin1 is rapidly dephosphorylated, a process that is required for its clathrin binding and receptor endocytosis but not for its receptor binding and desensitization. Once internalized, beta-arrestin1 is rephosphorylated. Thus, as with the classical endocytic adaptor protein complex AP2, beta-arrestin1 functions as a clathrin adaptor in receptor endocytosis which is regulated by dephosphorylation at the plasma membrane.

Full Text

Duke Authors

Cited Authors

  • Lin, FT; Krueger, KM; Kendall, HE; Daaka, Y; Fredericks, ZL; Pitcher, JA; Lefkowitz, RJ

Published Date

  • December 5, 1997

Published In

Volume / Issue

  • 272 / 49

Start / End Page

  • 31051 - 31057

PubMed ID

  • 9388255

Pubmed Central ID

  • 9388255

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.272.49.31051

Language

  • eng

Conference Location

  • United States