Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding Journal Article
| Authors: | Hacisuleyman, E.; Hale, C. R.; Noble, N.; Luo, J. D.; Fak, J. J.; Saito, M.; Chen, J.; Weissman, J. S.; Darnell, R. B. |
| Article Title: | Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding |
| Abstract: | Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear. In this study, to monitor how depolarization impacts local dendritic biology, we employed a dendritically targeted proximity labeling approach followed by crosslinking immunoprecipitation, ribosome profiling and mass spectrometry. Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG caused rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated. For a subset of pre-localized messages, depolarization increased the translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long-term potentiation, cell signaling and energy metabolism. This activity-dependent translation was accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs were sufficient to confer depolarization-induced, eIF4G2-dependent translational control. These studies uncovered an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling. © The Author(s) 2024. |
| Keywords: | signal transduction; controlled study; protein expression; human cell; genetics; nonhuman; flow cytometry; translation initiation; cell proliferation; mass spectrometry; quality control; animal cell; mouse; animal; metabolism; animals; mice; cells, cultured; immune system; gene expression; nuclear protein; animal model; neurons; immunofluorescence; phosphorylation; physiology; cell culture; protein synthesis; nucleotide sequence; rat; western blotting; immunoprecipitation; protein biosynthesis; rats; upregulation; doxycycline; cytoskeleton; nerve cell; energy metabolism; transcriptome; streptavidin; dendrite; dendrites; biotinylation; open reading frame; calcium transport; open reading frames; potassium chloride; myristylation; synaptosome; initiation factor 4g; human; article; eukaryotic initiation factor-4g; depolarization; gene set enrichment analysis |
| Journal Title: | Nature Neuroscience |
| Volume: | 27 |
| Issue: | 5 |
| ISSN: | 1097-6256 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-05-01 |
| Start Page: | 822 |
| End Page: | 835 |
| Language: | English |
| DOI: | 10.1038/s41593-024-01615-5 |
| PUBMED: | 38589584 |
| PROVIDER: | scopus |
| PMCID: | PMC11088998 |
| DOI/URL: | |
| Notes: | Source: Scopus |
