Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/102873
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Type: Journal article
Title: Two-stage translational control of dentate gyrus LTP consolidation is mediated by sustained BDNF-TrkB signaling to MNK
Author: Panja, D.
Kenney, J.
D'Andrea, L.
Zalfa, F.
Vedeler, A.
Wibrand, K.
Fukunaga, R.
Bagni, C.
Proud, C.
Bramham, C.
Citation: Cell Reports, 2014; 9(4):1430-1445
Publisher: Cell Press
Issue Date: 2014
ISSN: 2211-1247
2211-1247
Statement of
Responsibility: 
Debabrata Panja, Justin W. Kenney, Laura D’Andrea, Francesca Zalfa, Anni Vedeler, Karin Wibrand, Rikiro Fukunaga, Claudia Bagni, Christopher G. Proud, and Clive R. Bramham
Abstract: BDNF signaling contributes to protein-synthesis-dependent synaptic plasticity, but the dynamics of TrkB signaling and mechanisms of translation have not been defined. Here, we show that long-term potentiation (LTP) consolidation in the dentate gyrus of live rodents requires sustained (hours) BDNF-TrkB signaling. Surprisingly, this sustained activation maintains an otherwise labile signaling pathway from TrkB to MAP-kinase-interacting kinase (MNK). MNK activity promotes eIF4F translation initiation complex formation and protein synthesis in mechanistically distinct early and late stages. In early-stage translation, MNK triggers release of the CYFIP1/FMRP repressor complex from the 5'-mRNA cap. In late-stage translation, MNK regulates the canonical translational repressor 4E-BP2 in a synapse-compartment-specific manner. This late stage is coupled to MNK-dependent enhanced dendritic mRNA translation. We conclude that LTP consolidation in the dentate gyrus is mediated by sustained BDNF signaling to MNK and MNK-dependent regulation of translation in two functionally and mechanistically distinct stages.
Keywords: Dentate Gyrus
Rights: © 2014 The Authors
RMID: 0030028845
DOI: 10.1016/j.celrep.2014.10.016
Appears in Collections:Molecular and Biomedical Science publications

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