The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP.
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The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. / Napoli, Ilaria; Mercaldo, Valentina; Boyl, Pietro Pilo; Eleuteri, Boris; Zalfa, Francesca; Silvia, De Rubeis; Daniele, Di Marino; Mohr, Evita; Massimi, Marzia; Falconi, Mattia; Witke, Walter; Costa-Mattioli, Mauro; Sonenberg, Nahum; Achsel, Tilmann; Bagni, Claudia.
in: CELL, Jahrgang 134, Nr. 6, 6, 2008, S. 1042-1054.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP.
AU - Napoli, Ilaria
AU - Mercaldo, Valentina
AU - Boyl, Pietro Pilo
AU - Eleuteri, Boris
AU - Zalfa, Francesca
AU - Silvia, De Rubeis
AU - Daniele, Di Marino
AU - Mohr, Evita
AU - Massimi, Marzia
AU - Falconi, Mattia
AU - Witke, Walter
AU - Costa-Mattioli, Mauro
AU - Sonenberg, Nahum
AU - Achsel, Tilmann
AU - Bagni, Claudia
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 134
SP - 1042
EP - 1054
JO - CELL
JF - CELL
SN - 0092-8674
IS - 6
M1 - 6
ER -