Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity

The time of day strongly influences adaptive behaviors like long-term memory, but the correlating synaptic and molecular mechanisms remain unclear. The circadian clock comprises a canonical transcription-translation feedback loop (TTFL) strictly dependent on the BMAL1 transcription factor. We report...

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Detalles Bibliográficos
Autores principales: Barone, Ilaria, Gilette, Nicole M., Hawks-Mayer, Hannah, Handy, Jonathan, Zhang, Kevin J., Chifamba, Fortunate F., Mostafa, Engie, Johnson-Venkatesh, Erin M., Sun, Yan, Gibson, Jennifer M., Rotenberg, Alexander, Umemori, Hisashi, Tsai, Peter T., Lipton, Jonathan O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Neuroscience
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599629/
https://www.ncbi.nlm.nih.gov/pubmed/37878694
http://dx.doi.org/10.1126/sciadv.adj1010
Descripción
Sumario:The time of day strongly influences adaptive behaviors like long-term memory, but the correlating synaptic and molecular mechanisms remain unclear. The circadian clock comprises a canonical transcription-translation feedback loop (TTFL) strictly dependent on the BMAL1 transcription factor. We report that BMAL1 rhythmically localizes to hippocampal synapses in a manner dependent on its phosphorylation at Ser(42) [pBMAL1(S42)]. pBMAL1(S42) regulates the autophosphorylation of synaptic CaMKIIα and circadian rhythms of CaMKIIα-dependent molecular interactions and LTP but not global rest/activity behavior. Therefore, our results suggest a model in which repurposing of the clock protein BMAL1 to synapses locally gates the circadian timing of plasticity.

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