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 M. Johnson-Venkatesh; Yan Sun; Jennifer M. Gibson; Alexander Rotenberg; Hisashi Umemori; Peter T. Tsai; Jonathan O. Lipton

doi:10.1126/SCIADV.ADJ1010

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 M. Johnson-Venkatesh, Yan Sun, Jennifer M. Gibson, Alexander Rotenberg, Hisashi Umemori, Peter T. Tsai, Jonathan O. Lipton

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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 lo-calizes 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.

Original language	English (US)
Article number	adj1010
Journal	Science Advances
Volume	9
Issue number	43
DOIs	https://doi.org/10.1126/SCIADV.ADJ1010
State	Published - 2023

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title = "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 lo-calizes 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.",

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

note = "Publisher Copyright: {\textcopyright} 2023 The Authors, some rights reserved.",

year = "2023",

doi = "10.1126/SCIADV.ADJ1010",

language = "English (US)",

volume = "9",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "43",

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T1 - Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity

AU - Barone, Ilaria

AU - Gilette, Nicole M.

AU - Hawks-Mayer, Hannah

AU - Handy, Jonathan

AU - Zhang, Kevin J.

AU - Chifamba, Fortunate F.

AU - Mostafa, Engie

AU - Johnson-Venkatesh, Erin M.

AU - Sun, Yan

AU - Gibson, Jennifer M.

AU - Rotenberg, Alexander

AU - Umemori, Hisashi

AU - Tsai, Peter T.

AU - Lipton, Jonathan O.

PY - 2023

Y1 - 2023

N2 - 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 lo-calizes 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.

AB - 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 lo-calizes 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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DO - 10.1126/SCIADV.ADJ1010

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JO - Science Advances

JF - Science Advances

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Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity

Abstract

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