PKA-dependent phosphorylation of ribosomal protein S6 does not correlate with translation efficiency in striatonigral and striatopallidal medium-sized spiny neurons

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Anne BieverEmmanuel Valjent

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 be...Continue Reading

Citations

Sep 1, 2015·Neuropharmacology·Laurie P Sutton, Marc G Caron
Jan 7, 2016·Frontiers in Molecular Neuroscience·Anne BieverEmma Puighermanal
Jul 26, 2015·Progress in Neurobiology·Matthieu F BastideErwan Bézard
May 24, 2016·Genes, Brain, and Behavior·A E ArrantE D Roberson
Jan 10, 2018·Frontiers in Molecular Neuroscience·Emma PuighermanalEmmanuel Valjent
Jul 5, 2019·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Sophie Laguesse, Dorit Ron
Jun 28, 2019·Journal of Neurochemistry·Giuseppe GangarossaEmmanuel Valjent
Nov 1, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aurélie TréfierPascale Crépieux
Apr 18, 2018·Molecular Neurobiology·Ilaria BaroneMargherita Maffei
Jan 29, 2019·Frontiers in Pharmacology·Daniel García-RincónIsmael Galve-Roperh
May 20, 2016·Learning & Memory·Patricia Salgado PirbhoyOswald Steward
Nov 7, 2017·Frontiers in Molecular Neuroscience·Laura CeolinEmma Puighermanal
Feb 1, 2020·Science·Anne BieverErin M Schuman
Apr 25, 2020·Nature Communications·Emma PuighermanalEmmanuel Valjent
Jun 6, 2020·Frontiers in Molecular Neuroscience·Orit DavidKobi Rosenblum
Dec 29, 2020·Addiction Biology·Laura CutandoEmmanuel Valjent
Nov 28, 2020·Trends in Neurosciences·Emmanuel Valjent, Giuseppe Gangarossa

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