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Gene Review

Rgs9  -  regulator of G-protein signaling 9

Mus musculus

Synonyms: RGS9, RGS9-1, Regulator of G-protein signaling 9, Rgs9-2
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Disease relevance of Rgs9


High impact information on Rgs9

  • The long RGS9 isoform contains a C-terminal domain that provides high-affinity interaction with its target G protein [2].
  • RGS9 modulates dopamine signaling in the basal ganglia [3].
  • Conversely, RGS9 knockout mice showed heightened locomotor and rewarding responses to cocaine and related psychostimulants [3].
  • Our study of two splice isoforms of RGS9 expressed in different types of neurons revealed a novel mechanism whereby this specificity is determined by specialized protein domains or subunits acting as affinity adapters [2].
  • RGS9, a GTPase accelerator for phototransduction [4].

Chemical compound and disease context of Rgs9


Biological context of Rgs9

  • In the present study we identify a novel splice variant of RGS9, RGS9-2, cloned from a mouse forebrain cDNA library, which encodes a striatal-specific isoform of the protein [5].
  • The minimal structure within the RGS9-1.Gbeta5L complex capable of activating transducin GTPase is the catalytic domain of RGS9 [6].

Anatomical context of Rgs9


Associations of Rgs9 with chemical compounds

  • Morphine treatment increased the EC50 (6.2-fold) for DAMGO-mediated inhibition of forskolin-stimulated cAMP activity in control cells but not in cells treated with AS-114 to knock-down RGS9 [10].

Other interactions of Rgs9

  • This effect was a consequence of the complete absence of any detectable RGS9 from the retinas of R9AP knockout mice [11].
  • An illumination threshold for the Gtalpha movement out of the OS is lower in the RGS9 knockout mice, indicating that the fast inactivation of transducin in the wild-type mice limits its translocation to the IS/ST [12].
  • We found that light responses from R9AP knockout rods were very slow to recover and were indistinguishable from those of RGS9 or Gbeta5 knockout rods [11].

Analytical, diagnostic and therapeutic context of Rgs9

  • Mice lacking RGS9 show enhanced behavioral responses to acute and chronic morphine, including a dramatic increase in morphine reward, increased morphine analgesia with delayed tolerance, and exacerbated morphine physical dependence and withdrawal [7].


  1. D2 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. 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. J. Neurosci. (2005) [Pubmed]
  2. Specificity of G protein-RGS protein recognition is regulated by affinity adapters. Martemyanov, K.A., Hopp, J.A., Arshavsky, V.Y. Neuron (2003) [Pubmed]
  3. RGS9 modulates dopamine signaling in the basal ganglia. Rahman, Z., Schwarz, J., Gold, S.J., Zachariou, V., Wein, M.N., Choi, K.H., Kovoor, A., Chen, C.K., DiLeone, R.J., Schwarz, S.C., Selley, D.E., Sim-Selley, L.J., Barrot, M., Luedtke, R.R., Self, D., Neve, R.L., Lester, H.A., Simon, M.I., Nestler, E.J. Neuron (2003) [Pubmed]
  4. RGS9, a GTPase accelerator for phototransduction. He, W., Cowan, C.W., Wensel, T.G. Neuron (1998) [Pubmed]
  5. Cloning and characterization of RGS9-2: a striatal-enriched alternatively spliced product of the RGS9 gene. Rahman, Z., Gold, S.J., Potenza, M.N., Cowan, C.W., Ni, Y.G., He, W., Wensel, T.G., Nestler, E.J. J. Neurosci. (1999) [Pubmed]
  6. Noncatalytic domains of RGS9-1.Gbeta 5L play a decisive role in establishing its substrate specificity. Martemyanov, K.A., Arshavsky, V.Y. J. Biol. Chem. (2002) [Pubmed]
  7. Essential role for RGS9 in opiate action. Zachariou, V., Georgescu, D., Sanchez, N., Rahman, Z., DiLeone, R., Berton, O., Neve, R.L., Sim-Selley, L.J., Selley, D.E., Gold, S.J., Nestler, E.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. R7BP, a novel neuronal protein interacting with RGS proteins of the R7 family. Martemyanov, K.A., Yoo, P.J., Skiba, N.P., Arshavsky, V.Y. J. Biol. Chem. (2005) [Pubmed]
  9. Differential expression of regulator of G-protein signalling transcripts and in vivo migration of CD4+ naïve and regulatory T cells. Agenès, F., Bosco, N., Mascarell, L., Fritah, S., Ceredig, R. Immunology (2005) [Pubmed]
  10. Opioid peptide receptor studies. 17. Attenuation of chronic morphine effects after antisense oligodeoxynucleotide knock-down of RGS9 protein in cells expressing the cloned Mu opioid receptor. Xu, H., Wang, X., Wang, J., Rothman, R.B. Synapse (2004) [Pubmed]
  11. Absence of the RGS9.Gbeta5 GTPase-activating complex in photoreceptors of the R9AP knockout mouse. Keresztes, G., Martemyanov, K.A., Krispel, C.M., Mutai, H., Yoo, P.J., Maison, S.F., Burns, M.E., Arshavsky, V.Y., Heller, S. J. Biol. Chem. (2004) [Pubmed]
  12. Transducin activation state controls its light-dependent translocation in rod photoreceptors. Kerov, V., Chen, D., Moussaif, M., Chen, Y.J., Chen, C.K., Artemyev, N.O. J. Biol. Chem. (2005) [Pubmed]
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