RGS9-2 mediates specific inhibition of agonist-induced internalization of D2-dopamine receptors

J Neurochem. 2010 Aug;114(3):739-49. doi: 10.1111/j.1471-4159.2010.06805.x. Epub 2010 May 8.


Regulator of G protein signaling 9-2 (RGS9-2), a member of the RGS family of GTPase accelerating proteins, is expressed specifically in the striatum, a brain region involved in controlling movement, motivation, mood and addiction. RGS9-2 can be found co-localized with D(2)-class dopamine receptors in medium spiny striatal neurons and altered functioning of both RGS9-2 and D(2)-like dopamine receptors have been implicated in schizophrenia, movement disorders and reward responses. Previously we showed that RGS9-2 can specifically co-localize with D(2)-dopamine receptors (D2R). Here we provide further evidence of the specificity of RGS9-2 for regulating D2R cellular functions: the expression of RGS9-2 inhibits dopamine-mediated cellular internalization of D2R, while the expression of another RGS protein, RGS4, had no effect. In addition, the agonist-mediated internalization of the G protein coupled delta opioid receptor was unaffected by RGS9-2 expression. We utilized mutant constructs of RGS9-2 to show that the RGS9-2 DEP (for Disheveled, EGL-10, Pleckstrin homology) domain and the GTPase accelerating activity of RGS9-2 were necessary for mediating specific inhibition of D2R internalization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Dopamine / physiology
  • Dopamine Agonists / pharmacology*
  • Dopamine D2 Receptor Antagonists*
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Female
  • Humans
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oocytes
  • Protein Structure, Tertiary / drug effects
  • Protein Structure, Tertiary / physiology
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • RGS Proteins / chemistry
  • RGS Proteins / metabolism
  • RGS Proteins / physiology*
  • Receptors, Dopamine D2 / metabolism*
  • Xenopus laevis


  • Dopamine Agonists
  • Dopamine D2 Receptor Antagonists
  • RGS Proteins
  • Receptors, Dopamine D2
  • regulator of g-protein signaling 9
  • Dopamine