The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP.
Cell
; 134(6): 1042-54, 2008 Sep 19.
Article
em En
| MEDLINE
| ID: mdl-18805096
ABSTRACT
Strong evidence indicates that regulated mRNA translation in neuronal dendrites underlies synaptic plasticity and brain development. The fragile X mental retardation protein (FMRP) is involved in this process; here, we show that it acts by inhibiting translation initiation. A binding partner of FMRP, CYFIP1/Sra1, directly binds the translation initiation factor eIF4E through a domain that is structurally related to those present in 4E-BP translational inhibitors. Brain cytoplasmic RNA 1 (BC1), another FMRP binding partner, increases the affinity of FMRP for the CYFIP1-eIF4E complex in the brain. Levels of proteins encoded by known FMRP target mRNAs are increased upon reduction of CYFIP1 in neurons. Translational repression is regulated in an activity-dependent manner because BDNF or DHPG stimulation of neurons causes CYFIP1 to dissociate from eIF4E at synapses, thereby resulting in protein synthesis. Thus, the translational repression activity of FMRP in the brain is mediated, at least in part, by CYFIP1.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biossíntese de Proteínas
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Encéfalo
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Proteína do X Frágil da Deficiência Intelectual
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Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article