Journal
FRONTIERS IN MOLECULAR NEUROSCIENCE
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2017.00419
Keywords
mRNA translation; striatum; LTP (long-term potentiation); ribosomal proteins; rpS6 phosphorylation
Categories
Funding
- Inserm
- Fondation pour la Recherche Medicale
- Sinergia grant of the Swiss NSF [CRSII3_154411]
- NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation
- Marie Curie Intra-European Fellowship [IEF327648]
- Fonds National de la Recherche, Luxembourg [3977033]
- LABEX EpiGenMed (Investissements d'avenir) [ANR-10-LABX-12-01]
- Swiss National Science Foundation (SNF) [CRSII3_154411] Funding Source: Swiss National Science Foundation (SNF)
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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.
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