Two-stage translational control of dentate gyrus LTP consolidation is mediated by sustained BDNF-TrkB signaling to MNK
Panja, Debabrata; Kenney, Justin W.; D'Andrea, Laura; Zalfa, Francesca; Vedeler, Anni; Wibrand, Karin; Fukunaga, Rikiro; Bagni, Claudia; Proud, Christopher G.; Bramham, Clive R.
Peer reviewed, Journal article
Published version
Permanent lenke
https://hdl.handle.net/1956/9548Utgivelsesdato
2014-11-20Metadata
Vis full innførselSamlinger
Originalversjon
https://doi.org/10.1016/j.celrep.2014.10.016Sammendrag
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.