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Dopamine D2 Receptor Relies upon PPM/PP2C Protein Phosphatases to Dephosphorylate Huntingtin Protein |
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| Authors: | Sébastien Marion Nikhil M Urs Sean M Peterson Tatyana D Sotnikova Jean-Martin Beaulieu Raul R Gainetdinov Marc G Caron |
| Institution: | From the Departments of ‡Cell Biology.;‖Medicine, and ;**Neurobiology Duke University Medical Center, Durham, North Carolina 27710.;the §Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval/IUSMQ, Québec G1J 2G3, Canada, and ;the ¶Department of Neuroscience, Italian Institute of Technology, 16163 Genova, Italy |
| Abstract: | 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. |
| Keywords: | Akt Arrestin Dopamine Receptors G Protein-coupled Receptors (GPCR) G Proteins Phosphatase PP2C Dopamine D2 Receptor Huntingtin |