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.
CEINGE Biotecnologie Avanzate, Naples, Italy.
Francesco
F
Errico
Emanuela
E
Santini
Sara
S
Migliarini
Anders
A
Borgkvist
Diego
D
Centonze
Valentina
V
Nasti
Manolo
M
Carta
Valentina
V
De Chiara
Chiara
C
Prosperetti
Daniela
D
Spano
Denis
D
Herve
Massimo
M
Pasqualetti
Roberto
R
Di Lauro
Gilberto
G
Fisone
Alessandro
A
Usiello
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