Title: The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP
Authors: Napoli, Ilaria ×
Mercaldo, Valentina
Boyl, Pietro Pilo
Eleuteri, Boris
Zalfa, Francesca
De Rubeis, Silvia
Di Marino, Daniele
Mohr, Evita
Massimi, Marzia
Falconi, Mattia
Witke, Walter
Costa-Mattioli, Mauro
Sonenberg, Nahum
Achsel, Tilmann
Bagni, Claudia #
Issue Date: Sep-2008
Publisher: MIT Press
Series Title: Cell vol:134 issue:6 pages:1042-54
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.
ISSN: 0092-8674
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Molecular Genetics Section (-)
Laboratory for the Research of Neurodegenerative Diseases
Laboratory for Molecular Neurobiology
× corresponding author
# (joint) last author

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