| Title | The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability |
|---|---|
| Publication Type | Articolo su Rivista peer-reviewed |
| Year of Publication | 2024 |
| Authors | Mollinari, Cristiana, Cardinale Alessio, Lupacchini Leonardo, Martire Alberto, Chiodi Valentina, Martinelli Andrea, Rinaldi Anna Maria, Fini Massimo, Pazzaglia Simonetta, Domenici Maria Rosaria, Garaci Enrico, and Merlo Daniela |
| Journal | EMBO Reports |
| Volume | 25 |
| Pagination | 3707 – 3737 |
| Type of Article | Article |
| ISSN | 1469221X |
| Abstract | The key DNA repair enzyme DNA-PKcs has several and important cellular functions. Loss of DNA-PKcs activity in mice has revealed essential roles in immune and nervous systems. In humans, DNA-PKcs is a critical factor for brain development and function since mutation of the prkdc gene causes severe neurological deficits such as microcephaly and seizures, predicting yet unknown roles of DNA-PKcs in neurons. Here we show that DNA-PKcs modulates synaptic plasticity. We demonstrate that DNA-PKcs localizes at synapses and phosphorylates PSD-95 at newly identified residues controlling PSD-95 protein stability. DNA-PKcs −/− mice are characterized by impaired Long-Term Potentiation (LTP), changes in neuronal morphology, and reduced levels of postsynaptic proteins. A PSD-95 mutant that is constitutively phosphorylated rescues LTP impairment when over-expressed in DNA-PKcs −/− mice. Our study identifies an emergent physiological function of DNA-PKcs in regulating neuronal plasticity, beyond genome stability. © The Author(s) 2024. |
| Notes | Cited by: 0; All Open Access, Green Open Access |
| URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85200893975&doi=10.1038%2fs44319-024-00198-3&partnerID=40&md5=cea8a9b6d79aafb80565380fb4e43052 |
| DOI | 10.1038/s44319-024-00198-3 |
| Citation Key | Mollinari20243707 |
| PubMed ID | 39085642 |
