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

Errico, Francesco; Santini, Emanuela; Migliarini, Sara; Borgkvist, Anders; Centonze, Diego; Nasti, Valentina; Carta, Manolo LU ; De Chiara, Valentina; Prosperetti, Chiara and Spano, Daniela, et al. (2008) In Molecular and Cellular Neuroscience 37(2). p.335-345
Abstract
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... (More)
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. (Less)
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publication status
published
subject
keywords
signal, knockout mice, striatum, G-protien coupled receptor, dopamine, transduction, medium spiny neurons
in
Molecular and Cellular Neuroscience
volume
37
issue
2
pages
335 - 345
publisher
Elsevier
external identifiers
  • wos:000253226500013
  • scopus:38649098428
ISSN
1044-7431
DOI
10.1016/j.mcn.2007.10.007
language
English
LU publication?
yes
id
066bd8c2-7719-4060-ad52-f159f8e3ec56 (old id 1196401)
date added to LUP
2008-09-10 11:15:23
date last changed
2017-08-06 03:36:05
@article{066bd8c2-7719-4060-ad52-f159f8e3ec56,
  abstract     = {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.},
  author       = {Errico, Francesco and Santini, Emanuela and Migliarini, Sara and Borgkvist, Anders and Centonze, Diego and Nasti, Valentina and Carta, Manolo and De Chiara, Valentina and Prosperetti, Chiara and Spano, Daniela and Herve, Denis and Pasqualetti, Massimo and Di Lauro, Roberto and Fisone, Gilberto and Usiello, Alessandro},
  issn         = {1044-7431},
  keyword      = {signal,knockout mice,striatum,G-protien coupled receptor,dopamine,transduction,medium spiny neurons},
  language     = {eng},
  number       = {2},
  pages        = {335--345},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Neuroscience},
  title        = {The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons},
  url          = {http://dx.doi.org/10.1016/j.mcn.2007.10.007},
  volume       = {37},
  year         = {2008},
}