Two-Stage Translational Control of Dentate Gyrus LTP Consolidation Is Mediated by Sustained BDNF-TrkB Signaling to MNK

Debabrata Panja, Justin W. Kenney, Laura D'Andrea, Francesca Zalfa, Anni Vedeler, Karin Wibrand, Rikiro Fukunaga, Claudia Bagni, Christopher G. Proud, Clive R. Bramham

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

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. Inlate-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.

Original languageEnglish
Pages (from-to)1430-1445
Number of pages16
JournalCell Reports
Volume9
Issue number4
DOIs
Publication statusPublished or Issued - 20 Nov 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this