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https://hdl.handle.net/2440/102873
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dc.contributor.author | Panja, D. | - |
dc.contributor.author | Kenney, J. | - |
dc.contributor.author | D'Andrea, L. | - |
dc.contributor.author | Zalfa, F. | - |
dc.contributor.author | Vedeler, A. | - |
dc.contributor.author | Wibrand, K. | - |
dc.contributor.author | Fukunaga, R. | - |
dc.contributor.author | Bagni, C. | - |
dc.contributor.author | Proud, C. | - |
dc.contributor.author | Bramham, C. | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | Cell Reports, 2014; 9(4):1430-1445 | - |
dc.identifier.issn | 2211-1247 | - |
dc.identifier.issn | 2211-1247 | - |
dc.identifier.uri | http://hdl.handle.net/2440/102873 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | 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 | - |
dc.language.iso | en | - |
dc.publisher | Cell Press | - |
dc.rights | © 2014 The Authors | - |
dc.source.uri | http://dx.doi.org/10.1016/j.celrep.2014.10.016 | - |
dc.subject | Dentate Gyrus | - |
dc.title | Two-stage translational control of dentate gyrus LTP consolidation is mediated by sustained BDNF-TrkB signaling to MNK | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1016/j.celrep.2014.10.016 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Proud, C. [0000-0003-0704-6442] | - |
Appears in Collections: | Aurora harvest 3 Molecular and Biomedical Science publications |
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