The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons.
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.
Errico
Francesco
F
CEINGE Biotecnologie Avanzate, Naples, Italy.
Santini
Emanuela
E
Migliarini
Sara
S
Borgkvist
Anders
A
Centonze
Diego
D
Nasti
Valentina
V
Carta
Manolo
M
De Chiara
Valentina
V
Prosperetti
Chiara
C
Spano
Daniela
D
Herve
Denis
D
Pasqualetti
Massimo
M
Di Lauro
Roberto
R
Fisone
Gilberto
G
Usiello
Alessandro
A
D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006948:Hyperkinesis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D010641:Phenotype; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D044385:GTP-Binding Protein alpha Subunits; D017448:Receptors, Dopamine D2; C084618:olfactory G protein subunit alpha olf; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; C488189:Rasd2 protein, mouse; D004298:Dopamine