Targeting of diacylglycerol degradation to M1 muscarinic receptors by beta-arrestins.

Published

Journal Article

Seven-transmembrane receptor (7TMR) signaling is transduced by second messengers such as diacylglycerol (DAG) generated in response to the heterotrimeric guanine nucleotide-binding protein Gq and is terminated by receptor desensitization and degradation of the second messengers. We show that beta-arrestins coordinate both processes for the Gq-coupled M1 muscarinic receptor. beta-Arrestins physically interact with diacylglycerol kinases (DGKs), enzymes that degrade DAG. Moreover, beta-arrestins are essential for conversion of DAG to phosphatidic acid after agonist stimulation, and this activity requires recruitment of the beta-arrestin-DGK complex to activated 7TMRs. The dual function of beta-arrestins, limiting production of diacylglycerol (by receptor desensitization) while enhancing its rate of degradation, is analogous to their ability to recruit adenosine 3',5'-monophosphate phosphodiesterases to Gs-coupled beta2-adrenergic receptors. Thus, beta-arrestins can serve similar regulatory functions for disparate classes of 7TMRs through structurally dissimilar enzymes that degrade chemically distinct second messengers.

Full Text

Duke Authors

Cited Authors

  • Nelson, CD; Perry, SJ; Regier, DS; Prescott, SM; Topham, MK; Lefkowitz, RJ

Published Date

  • February 2, 2007

Published In

Volume / Issue

  • 315 / 5812

Start / End Page

  • 663 - 666

PubMed ID

  • 17272726

Pubmed Central ID

  • 17272726

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1134562

Language

  • eng

Conference Location

  • United States