dc.contributor.author | Patil, Sudarshan | |
dc.contributor.author | Chalkiadaki, Kleanthi | |
dc.contributor.author | Mergiya, Tadiwos Feyissa | |
dc.contributor.author | Krimbacher, Konstanze | |
dc.contributor.author | Amorim, Inês S. | |
dc.contributor.author | Akerkar, Shreeram Rajendra | |
dc.contributor.author | Gkogkas, Christos G. | |
dc.contributor.author | Bramham, Clive Raymond Evjen | |
dc.date.accessioned | 2024-08-05T11:24:15Z | |
dc.date.available | 2024-08-05T11:24:15Z | |
dc.date.created | 2023-05-11T13:41:52Z | |
dc.date.issued | 2023 | |
dc.identifier.issn | 2589-0042 | |
dc.identifier.uri | https://hdl.handle.net/11250/3144433 | |
dc.description.abstract | The mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is crucial for translation and regulated by Ser209 phosphorylation. However, the biochemical and physiological role of eIF4E phosphorylation in translational control of long-term synaptic plasticity is unknown. We demonstrate that phospho-ablated Eif4eS209A Knockin mice are profoundly impaired in dentate gyrus LTP maintenance in vivo, whereas basal perforant path-evoked transmission and LTP induction are intact. mRNA cap-pulldown assays show that phosphorylation is required for synaptic activity-induced removal of translational repressors from eIF4E, allowing initiation complex formation. Using ribosome profiling, we identified selective, phospho-eIF4E-dependent translation of the Wnt signaling pathway in LTP. Surprisingly, the canonical Wnt effector, β-catenin, was massively recruited to the eIF4E cap complex following LTP induction in wild-type, but not Eif4eS209A, mice. These results demonstrate a critical role for activity-evoked eIF4E phosphorylation in dentate gyrus LTP maintenance, remodeling of the mRNA cap-binding complex, and specific translation of the Wnt pathway. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Cell Press | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | eIF4E phosphorylation recruits β-catenin to mRNA cap and promotes Wnt pathway translation in dentate gyrus LTP maintenance | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2023 The Author(s) | en_US |
dc.source.articlenumber | 106649 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.1016/j.isci.2023.106649 | |
dc.identifier.cristin | 2146962 | |
dc.source.journal | iScience | en_US |
dc.identifier.citation | iScience. 2023, 26 (5), 106649. | en_US |
dc.source.volume | 26 | en_US |
dc.source.issue | 5 | en_US |