Reactivation of stalled polyribosomes in synaptic plasticity.
Proc Natl Acad Sci U S A
; 110(40): 16205-10, 2013 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-24043809
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Polirribossomos
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Sinapses
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RNA Mensageiro
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Regulação da Expressão Gênica
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Plasticidade Neuronal
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Neurônios
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article