Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity.

Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity.
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DOI:
10.1126/sciadv.adj1010
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发表时间:
2023-10-27
期刊:
影响因子:
13.6
通讯作者:
Lipton, Jonathan O.
Lipton, Jonathan O.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
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.

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一天中的时间强烈影响适应行为,如长期记忆,但相关的突触和分子机制尚不清楚。生物钟包括一个严格依赖于BMAL1转录因子的典型转录-翻译反馈回路(TTFL)。我们报道BMAL1以一种依赖于其Ser42磷酸化的方式有节律地定位于海马突触[pBMAL1(S42)]。pBMAL1(S42)调节突触CaMKIIα的自磷酸化和CaMKIIα依赖的分子相互作用和LTP的昼夜节律,但不调节整体休息/活动行为。因此,我们的研究结果提出了一个模型,在这个模型中,时钟蛋白BMAL1对突触的重新利用局部控制了可塑性的昼夜节律。昼夜节律蛋白BMAL1有节律地定位于突触,对突触可塑性的相应节律至关重要。
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. The circadian protein BMAL1 rhythmically localizes to synapses and is crucial for corresponding rhythms in synaptic plasticity.
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