S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking.

Published

Journal Article

Signal transduction through G protein-coupled receptors (GPCRs) is regulated by receptor desensitization and internalization that follow agonist stimulation. Nitric oxide (NO) can influence these processes, but the cellular source of NO bioactivity and the effects of NO on GPCR-mediated signal transduction are incompletely understood. Here, we show in cells and mice that beta-arrestin 2, a central element in GPCR trafficking, interacts with and is S-nitrosylated at a single cysteine by endothelial NO synthase (eNOS), and that S-nitrosylation of beta-arrestin 2 is promoted by endogenous S-nitrosogluthathione. S-nitrosylation after agonist stimulation of the beta-adrenergic receptor, a prototypical GPCR, dissociates eNOS from beta-arrestin 2 and promotes binding of beta-arrestin 2 to clathrin heavy chain/beta-adaptin, thereby accelerating receptor internalization. The agonist- and NO-dependent shift in the affiliations of beta-arrestin 2 is followed by denitrosylation. Thus, beta-arrestin subserves the functional coupling of eNOS and GPCRs, and dynamic S-nitrosylation/denitrosylation of beta-arrestin 2 regulates stimulus-induced GPCR trafficking.

Full Text

Duke Authors

Cited Authors

  • Ozawa, K; Whalen, EJ; Nelson, CD; Mu, Y; Hess, DT; Lefkowitz, RJ; Stamler, JS

Published Date

  • August 8, 2008

Published In

Volume / Issue

  • 31 / 3

Start / End Page

  • 395 - 405

PubMed ID

  • 18691971

Pubmed Central ID

  • 18691971

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2008.05.024

Language

  • eng

Conference Location

  • United States