Ribosomal Protein S6 Phosphorylation Is Involved in Novelty-Induced Locomotion, Synaptic Plasticity and mRNA Translation.
Front. Mol. Neurosci.. 2017-12-21; 10:
DOI: 10.3389/fnmol.2017.00419
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1. Front Mol Neurosci. 2017 Dec 21;10:419. doi: 10.3389/fnmol.2017.00419.
eCollection 2017.
Ribosomal Protein S6 Phosphorylation Is Involved in Novelty-Induced Locomotion,
Synaptic Plasticity and mRNA Translation.
Puighermanal E(1), Biever A(1), Pascoli V(2), Melser S(3), Pratlong M(4), Cutando
L(1), Rialle S(4), Severac D(4), Boubaker-Vitre J(1), Meyuhas O(5), Marsicano
G(3), Lüscher C(2)(6), Valjent E(1).
Author information:
(1)IGF, CNRS, INSERM, University of Montpellier, Montpellier, France.
(2)Department of Basic Neurosciences, Medical Faculty, University of Geneva,
Geneva, Switzerland.
(3)INSERM U1215, Université de Bordeaux, NeuroCentre Magendie, Bordeaux, France.
(4)Montpellier GenomiX, BioCampus Montpellier, CNRS, INSERM, University of
Montpellier, Montpellier, France.
(5)Department of Biochemistry and Molecular Biology, IMRIC, The Hebrew
University-Hadassah Medical School, Jerusalem, Israel.
(6)Clinic of Neurology, Department of Clinical Neurosciences, Geneva University
Hospital, Geneva, Switzerland.
The phosphorylation of the ribosomal protein S6 (rpS6) is widely used to track
neuronal activity. Although it is generally assumed that rpS6 phosphorylation has
a stimulatory effect on global protein synthesis in neurons, its exact biological
function remains unknown. By using a phospho-deficient rpS6 knockin mouse model,
we directly tested the role of phospho-rpS6 in mRNA translation, plasticity and
behavior. The analysis of multiple brain areas shows for the first time that, in
neurons, phospho-rpS6 is dispensable for overall protein synthesis. Instead, we
found that phospho-rpS6 controls the translation of a subset of mRNAs in a
specific brain region, the nucleus accumbens (Acb), but not in the dorsal
striatum. We further show that rpS6 phospho-mutant mice display altered long-term
potentiation (LTP) in the Acb and enhanced novelty-induced locomotion.
Collectively, our findings suggest a previously unappreciated role of
phospho-rpS6 in the physiology of the Acb, through the translation of a selective
subclass of mRNAs, rather than the regulation of general protein synthesis.
DOI: 10.3389/fnmol.2017.00419
PMCID: PMC5742586
PMID: 29311811