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- Title
PKA-Dependent Phosphorylation of Ribosomal Protein S6 Does Not Correlate with Translation Efficiency in Striatonigral and Striatopallidal Medium-Sized Spiny Neurons.
- Authors
Biever, Anne; Puighermanal, Emma; Akinori Nishi; David, Alexandre; Panciatici, Claire; Longueville, Sophie; Xirodimas, Dimitris; Gangarossa, Giuseppe; Meyuhas, Oded; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel
- Abstract
Ribosomal protein S6 (rpS6), a component of the 40S ribosomal subunit, is phosphorylated on several residues in response to numerous stimuli. Although commonly used as a marker for neuronal activity, its upstream mechanisms of regulation are poorly studied and its role in protein synthesis remains largely debated. Here, we demonstrate that the psychostimulant D-amphetamine (D-amph) markedly increases rpS6 phosphorylation at Ser235/236 sites in both crude and synaptoneurosomalpreparations of the mouse striatum. This effect occurs selectively in D1R-expressing medium-sized spiny neurons (MSNs) and requires the cAMP/PKA/DARPP-32/PP-1 cascade, whereas it is independent of mTORC1/p70S6K, PKC, and ERK signaling. By developing a novel assay to label nascent peptidic chains, we show that the rpS6 phosphorylation induced in striatonigral MSNs by D-amph, as well as in striatopallidal MSNs by the antipsychotic haloperidol or in both subtypes by papaverine, is not correlated with the translation of global or 5' terminal oligopyrimidine tract mRNAs. Together, these results provide novel mechanistic insights into the in vivo regulation of the post-translational modification of rpS6 in the striatum and point out the lack of a relationship between PKA-dependent rpS6 phosphorylation and translation efficiency.
- Subjects
RIBOSOMAL proteins; PROTEIN synthesis; EXTRACELLULAR signal-regulated kinases; NEURAL transmission; PROTEIN expression; DOPAMINE; G protein coupled receptors; POST-translational modification
- Publication
Journal of Neuroscience, 2015, Vol 35, Issue 10, p4113
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3288-14.2015