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Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity.

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.

SUBMITTER: Barone I

PROVIDER: S-EPMC10599629 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity.

Barone Ilaria I Gilette Nicole M NM Hawks-Mayer Hannah H Handy Jonathan J Zhang Kevin J KJ Chifamba Fortunate F FF Mostafa Engie E Johnson-Venkatesh Erin M EM Sun Yan Y Gibson Jennifer M JM Rotenberg Alexander A Umemori Hisashi H Tsai Peter T PT Lipton Jonathan O JO

Science advances 20231025 43

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 CaM ...[more]

PMID: 37878694

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