title: Reactivation of stalled polyribosomes in synaptic plasticity.
abstract: Some forms of synaptic plasticity require rapid, local activation of protein synthesis. Although this is thought to reflect recruitment of mRNAs to free ribosomes, this would limit the speed and magnitude of translational activation. Here we provide compelling in situ evidence supporting an alternative model in which synaptic mRNAs are transported as stably paused polyribosomes. Remarkably, we show that metabotropic glutamate receptor activation allows the synthesis of proteins that lead to a functional long-term depression phenotype even when translation initiation has been greatly reduced. Thus, neurons evolved a unique mechanism to swiftly translate synaptic mRNAs into functional protein upon synaptic signaling using stalled polyribosomes to bypass the rate-limiting step of translation initiation. Because dysregulated plasticity is implicated in neurodevelopmental and psychiatric disorders such as fragile X syndrome, this work uncovers a unique translational target for therapies.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada, H3A 2B4.
authors.forename: Tyson E
authors.initials: TE
authors.lastname: Graber
authors.forename: Sarah
authors.initials: S
authors.lastname: Hébert-Seropian
authors.forename: Arkady
authors.initials: A
authors.lastname: Khoutorsky
authors.forename: Alexandre
authors.initials: A
authors.lastname: David
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Yewdell
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lacaille
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Sossin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010441:Peptide Chain Elongation, Translational / Q000502:physiology; D011132:Polyribosomes / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology*; D055366:Synaptic Potentials / Q000502:physiology
chemical_list: D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; C085284:microtubule-associated protein 1B
keywords: RNA granule; mGluR-LTD; microtubule-associated protein 1b; translation elongation
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