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PMID:18035555

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Citation

Errico, F, Santini, E, Migliarini, S, Borgkvist, A, Centonze, D, Nasti, V, Carta, M, De Chiara, V, Prosperetti, C, Spano, D, Herve, D, Pasqualetti, M, Di Lauro, R, Fisone, G and Usiello, A (2008) The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons. Mol. Cell. Neurosci. 37:335-45

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.

Links

PubMed Online version:10.1016/j.mcn.2007.10.007

Keywords

Animals; Corpus Striatum/cytology; Corpus Striatum/metabolism; Cyclic AMP/metabolism; Cyclic AMP-Dependent Protein Kinases/metabolism; Dendritic Spines/metabolism; Dopamine/metabolism; Female; GTP-Binding Protein alpha Subunits/genetics; GTP-Binding Protein alpha Subunits/metabolism; GTP-Binding Proteins/genetics; GTP-Binding Proteins/metabolism; Hyperkinesis/genetics; Hyperkinesis/metabolism; Hyperkinesis/physiopathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation/genetics; Neurons/cytology; Neurons/metabolism; Organ Culture Techniques; Phenotype; Receptors, Dopamine D2/genetics; Receptors, Dopamine D2/metabolism; Signal Transduction/physiology; Synapses/metabolism; Synaptic Transmission/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:RHES

involved_in

GO:0001963: synaptic transmission, dopaminergic

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RHES

involved_in

GO:0007626: locomotory behavior

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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