Two-stage translational control of dentate gyrus LTP consolidation is mediated by sustained BDNF-TrkB signaling to MNK.

Authors: Panja, D  Kenney, JW  D'Andrea, L  Zalfa, F  Vedeler, A  Wibrand, K  Fukunaga, R  Bagni, C  Proud, CG  Bramham, CR 
Citation: Panja D, etal., Cell Rep. 2014 Nov 20;9(4):1430-45. doi: 10.1016/j.celrep.2014.10.016. Epub 2014 Nov 6.
Pubmed: (View Article at PubMed) PMID:25453757
DOI: Full-text: DOI:10.1016/j.celrep.2014.10.016

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.

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RGD ID: 11558007
Created: 2016-11-07
Species: All species
Last Modified: 2016-11-07
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.