PT  - JOURNAL ARTICLE
AU  - Kovoor, Abraham
AU  - Seyffarth, Petra
AU  - Ebert, Jana
AU  - Barghshoon, Sami
AU  - Chen, Ching-Kang
AU  - Schwarz, Sigrid
AU  - Axelrod, Jeffrey D.
AU  - Cheyette, Benjamin N. R.
AU  - Simon, Melvin I.
AU  - Lester, Henry A.
AU  - Schwarz, Johannes
TI  - D<sub>2</sub> Dopamine Receptors Colocalize Regulator of G-Protein Signaling 9-2 (RGS9-2) via the RGS9 DEP Domain, and RGS9 Knock-Out Mice Develop Dyskinesias Associated with Dopamine Pathways
AID  - 10.1523/JNEUROSCI.2840-04.2005
DP  - 2005 Feb 23
TA  - The Journal of Neuroscience
PG  - 2157--2165
VI  - 25
IP  - 8
4099  - http://www.jneurosci.org/content/25/8/2157.short
4100  - http://www.jneurosci.org/content/25/8/2157.full
SO  - J. Neurosci.2005 Feb 23; 25
AB  - Regulator of G-protein signaling 9-2 (RGS9-2), a member of the RGS family of Gα GTPase accelerating proteins, is expressed specifically in the striatum, which participates in antipsychotic-induced tardive dyskinesia and in levodopa-induced dyskinesia. We report that RGS9 knock-out mice develop abnormal involuntary movements when inhibition of dopaminergic transmission is followed by activation of D2-like dopamine receptors (DRs). These abnormal movements resemble drug-induced dyskinesia more closely than other rodent models. Recordings from striatal neurons of these mice establish that activation of D2-like DRs abnormally inhibits glutamate-elicited currents. We show that RGS9-2, via its DEP domain (for Disheveled, EGL-10, Pleckstrin homology), colocalizes with D2DRs when coexpressed in mammalian cells. Recordings from oocytes coexpressing D2DR or the m2 muscarinic receptor and G-protein-gated inward rectifier potassium channels show that RGS9-2, via its DEP domain, preferentially accelerates the termination of D2DR signals. Thus, alterations in RGS9-2 may be a key factor in the pathway leading from D2DRs to the side effects associated with the treatment both of psychoses and Parkinson's disease.