Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity
Ilaria Barone, Nicole M. Gilette, Hannah Hawks-Mayer, Jonathan Handy, Kevin J. Zhang, Fortunate F. Chifamba, Engie Mostafa, Erin Johnson‐Venkatesh, Yan Sun, Jennifer M. Gibson, Alexander Rotenberg, Hisashi Umemori, Peter T. Tsai, Jonathan O. Lipton
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 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.