The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons

Research output: Contribution to journalArticle


Rhes is a small GTP-binding protein prominently localized in the striatum. Previous findings obtained in cell culture systems demonstrated an involvement of Rhes in cAMP/PKA signalling pathway, at a level proximal to the activation of heterotrimeric G-protein complex. However, its role in the striatum has been, so far, only supposed. Here we studied the involvement of Rhes in dopaminergic signalling, by employing mice with a null mutation in the Rhes gene. We demonstrated that the absence of Rhes modulates cAMP/PKA signalling in both striatopallidal and striatonigral projection neurons by increasing Golf. protein levels and, in turn, influencing motor responses challenged by dopaminergic agonist/antagonist. Interestingly, we also show that Rhes is required for a correct dopamine-mediated GTP binding, a function mainly associated to stimulation of dopamine D2 receptors. Altogether, our results indicate that Rhes is an important modulator of dopaminergic transmission in the striatum.


  • Francesco Errico
  • Emanuela Santini
  • Sara Migliarini
  • Anders Borgkvist
  • Diego Centonze
  • Valentina Nasti
  • Manolo Carta
  • Valentina De Chiara
  • Chiara Prosperetti
  • Daniela Spano
  • Denis Herve
  • Massimo Pasqualetti
  • Roberto Di Lauro
  • Gilberto Fisone
  • Alessandro Usiello
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences


  • signal, knockout mice, striatum, G-protien coupled receptor, dopamine, transduction, medium spiny neurons
Original languageEnglish
Pages (from-to)335-345
JournalMolecular and Cellular Neuroscience
Issue number2
Publication statusPublished - 2008
Publication categoryResearch