S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking.
Journal Article (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
- PMC2630185
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