PKA-Dependent Phosphorylation of Ribosomal Protein S6 Does Not Correlate with Translation Efficiency in Striatonigral and Striatopallidal Medium-Sized Spiny Neurons
- Anne Biever1,2,3,*,
- Emma Puighermanal1,2,3,*,
- Akinori Nishi4,
- Alexandre David1,2,3,
- Claire Panciatici1,2,3,
- Sophie Longueville5,6,
- Dimitris Xirodimas7,
- Giuseppe Gangarossa1,2,3,
- Oded Meyuhas8,
- Denis Hervé5,6,
- Jean-Antoine Girault5,6, and
- Emmanuel Valjent1,2,3
- 1Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Montpellier, F-34094, France,
- 2INSERM, U1191, Montpellier, F-34094, France;
- 3Université de Montpellier, Montpellier, F-34094, France,
- 4Department of Pharmacology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan,
- 5Université Pierre et Marie Curie, INSERM UMR-S839, Paris, F-75005 France,
- 6Institut du Fer à Moulin, F-75005, Paris, France,
- 7Centre de Recherche en Biochimie Macromoléculaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5237, Montpellier, F-34000, France, and
- 8Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel–Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
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Author contributions: A.B., E.P., and E.V. designed research; A.B., E.P., A.N., C.P., S.L., G.G., and D.H. performed research; A.D., D.X., O.M., D.H., J.-A.G., and E.V. contributed unpublished reagents/analytic tools; A.B., E.P., A.N., C.P., and E.V. analyzed data; A.B., E.P., J.-A.G., and E.V. wrote the paper.
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↵*A.B. and E.P. contributed equally to this work.
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 synaptoneurosomal preparations 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.
- Received August 8, 2014.
- Revision received December 16, 2014.
- Accepted January 13, 2015.
- Copyright © 2015 the authors 0270-6474/15/354113-18$15.00/0
