Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity

Authors:

Ilaria Barone, Nicole M. Gilette, Hannah Hawks-Mayer, Jonathan Handy, Kevin J. Zhang, Fortunate F. Chifamba, Engie Mostafa, Erin M. Johnson-Venkatesh, Yan Sun, Jennifer M. Gibson, Alexander Rotenberg, Hisashi Umemori, Peter T. Tsai, Jonathan O. Lipton

Keywords:

circadian clock; transcription-translation feedback loop; TTFL; BMAL1, CaMKIIalpha

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 Ser⁴² [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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