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

Publication ,  Journal Article
Ozawa, K; Whalen, EJ; Nelson, CD; Mu, Y; Hess, DT; Lefkowitz, RJ; Stamler, JS
Published in: Mol Cell
August 8, 2008

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.

Duke Scholars

Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

August 8, 2008

Volume

31

Issue

3

Start / End Page

395 / 405

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • S-Nitrosothiols
  • Receptors, Adrenergic, beta-2
  • Protein Transport
  • Protein Binding
  • Nitroso Compounds
  • Nitric Oxide Synthase Type III
  • Models, Biological
  • Mice
 

Citation

APA
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Ozawa, K., Whalen, E. J., Nelson, C. D., Mu, Y., Hess, D. T., Lefkowitz, R. J., & Stamler, J. S. (2008). S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking. Mol Cell, 31(3), 395–405. https://doi.org/10.1016/j.molcel.2008.05.024
Ozawa, Kentaro, Erin J. Whalen, Christopher D. Nelson, Yuanyu Mu, Douglas T. Hess, Robert J. Lefkowitz, and Jonathan S. Stamler. “S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking.Mol Cell 31, no. 3 (August 8, 2008): 395–405. https://doi.org/10.1016/j.molcel.2008.05.024.
Ozawa K, Whalen EJ, Nelson CD, Mu Y, Hess DT, Lefkowitz RJ, et al. S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking. Mol Cell. 2008 Aug 8;31(3):395–405.
Ozawa, Kentaro, et al. “S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking.Mol Cell, vol. 31, no. 3, Aug. 2008, pp. 395–405. Pubmed, doi:10.1016/j.molcel.2008.05.024.
Ozawa K, Whalen EJ, Nelson CD, Mu Y, Hess DT, Lefkowitz RJ, Stamler JS. S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking. Mol Cell. 2008 Aug 8;31(3):395–405.

Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

August 8, 2008

Volume

31

Issue

3

Start / End Page

395 / 405

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • S-Nitrosothiols
  • Receptors, Adrenergic, beta-2
  • Protein Transport
  • Protein Binding
  • Nitroso Compounds
  • Nitric Oxide Synthase Type III
  • Models, Biological
  • Mice