Cancer Institute A national cancer institute
designated cancer center

Jeffrey Axelrod

Publication Details

  • D-2 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 JOURNAL OF NEUROSCIENCE Kovoor, A., Seyffarth, P., Ebert, J., Barghshoon, S., Chen, C. K., Schwarz, S., Axelrod, J. D., Cheyette, B. N., Simon, M. I., Lester, H. A., Schwarz, J. 2005; 25 (8): 2157-2165

    Abstract:

    Regulator of G-protein signaling 9-2 (RGS9-2), a member of the RGS family of G 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.

    View details for DOI 10.1523/JNEUROSCI.2840-04.2005

    View details for Web of Science ID 000227211000030

    View details for PubMedID 15728856

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