Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/102873
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Two-stage translational control of dentate gyrus LTP consolidation is mediated by sustained BDNF-TrkB signaling to MNK |
Author: | Panja, D. Kenney, J. D'Andrea, L. Zalfa, F. Vedeler, A. Wibrand, K. Fukunaga, R. Bagni, C. Proud, C. Bramham, C. |
Citation: | Cell Reports, 2014; 9(4):1430-1445 |
Publisher: | Cell Press |
Issue Date: | 2014 |
ISSN: | 2211-1247 2211-1247 |
Statement of Responsibility: | 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 |
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. |
Keywords: | Dentate Gyrus |
Rights: | © 2014 The Authors |
DOI: | 10.1016/j.celrep.2014.10.016 |
Published version: | http://dx.doi.org/10.1016/j.celrep.2014.10.016 |
Appears in Collections: | Aurora harvest 3 Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.