Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity.

Barone, Ilaria; Gilette, Nicole M; Hawks-Mayer, Hannah; Handy, Jonathan; Zhang, Kevin J; Chifamba, Fortunate F; Mostafa, Engie; Johnson-Venkatesh, Erin M et al. · Sci Adv · 2023

basic_science · Level V

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Abstract

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<sup>42</sup> [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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