Persistent TrkB signaling to MNK activates a two-stage translational switch underlying in vivo LTP maintenance

• Autorzy: Bramham C.R
• Języki publikacji: EN

Abstrakty

EN

Long-term synaptic plasticity requires stimulus-evoked changes in protein translation. However, the dynamics of translational control post-stimulus are little understood. We report that LTP maintenance at excitatory synapses in live rats requires repetitive BDNF activation of TrkB over hours. TrkB signalling to the MAP kinase-interacting kinases (MNKs) mediates sustained eIF4F translation initiation complex formation through a two-stage mechanism. In early LTP maintenance, MNK triggers release of the CYFIP1/FMRP repressor complex from the 5’- mRNA cap, coupled to translation of FMRP-regulated mRNAs. In late LTP maintenance, MNK switches to regulate the canonical translational repressor 4E-BP2 specifically within the synaptic compartment. This delayed release of 4E-BP2 is associated with synapse-specific polyribosome formation and enhanced dendritic mRNA translation. In MNK knockout mice, both CYFIP1 and 4E-BP2 repressor complexes are disrupted. Hence, sustained TrkB-MNK signalling drives the sequential activation of distinct forms of cap-dependent translation, culminating in synapse-specific translation and LTP maintenance.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: Suppl.1
• Opis fizyczny: p.21

Twórcy

autor

Bramham C.R

• Department of Biomedicine and KG Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway