Dopamine D2 receptor relies upon PPM/PP2C protein phosphatases to dephosphorylate huntingtin protein.


Journal Article

Striatal dopamine D2 receptor (D2R) relies upon G protein- and β-arrestin-dependent signaling pathways to convey its action on motor control and behavior. Considering that D2R activation inhibits Akt in the striatum and that huntingtin physiological functions are affected by Akt phosphorylation, we sought to investigate whether D2R-mediated signaling could regulate huntingtin phosphorylation. We demonstrate that D2R activation decreases huntingtin phosphorylation on its Akt site. This dephosphorylation event depends upon the Gαi-dependent engagement of specific members of the protein phosphatase metallo-dependent (PPM/PP2C) family and is independent of β-arrestin 2. These observations identify the PPM/PP2C family as a mediator of G protein-coupled receptor signaling and thereby suggest a novel mechanism of dopaminergic signaling.

Full Text

Duke Authors

Cited Authors

  • Marion, S; Urs, NM; Peterson, SM; Sotnikova, TD; Beaulieu, J-M; Gainetdinov, RR; Caron, MG

Published Date

  • April 25, 2014

Published In

Volume / Issue

  • 289 / 17

Start / End Page

  • 11715 - 11724

PubMed ID

  • 24619418

Pubmed Central ID

  • 24619418

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M113.544312


  • eng

Conference Location

  • United States