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Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16205-10. doi: 10.1073/pnas.1307747110. Epub 2013 Sep 16.

Reactivation of stalled polyribosomes in synaptic plasticity.

Author information

1
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada, H3A 2B4.

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.

KEYWORDS:

RNA granule; mGluR-LTD; microtubule-associated protein 1b; translation elongation

PMID:
24043809
PMCID:
PMC3791775
DOI:
10.1073/pnas.1307747110
[Indexed for MEDLINE]
Free PMC Article

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