The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability

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 constitutively phos

ORGANISM(S): Mus musculus (mouse)

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PROVIDER: S-BSST1420 | biostudies-other |

SECONDARY ACCESSION(S): 1

REPOSITORIES: biostudies-other