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Decoupling PER phosphorylation, stability and rhythmic expression from circadian clock function by abolishing PER-CK1 interaction

Author

Listed:
  • Yang An

    (Nanjing University
    Soochow University)

  • Baoshi Yuan

    (Soochow University)

  • Pancheng Xie

    (Soochow University
    University of Texas Southwestern Medical Center)

  • Yue Gu

    (Soochow University)

  • Zhiwei Liu

    (Soochow University)

  • Tao Wang

    (Soochow University)

  • Zhihao Li

    (Soochow University)

  • Ying Xu

    (Soochow University)

  • Yi Liu

    (University of Texas Southwestern Medical Center)

Abstract

Robust rhythms of abundances and phosphorylation profiles of PERIOD proteins were thought be the master rhythms that drive mammalian circadian clock functions. PER stability was proposed to be a major determinant of period length. In mammals, CK1 forms stable complexes with PER. Here we identify the PER residues essential for PER-CK1 interaction. In cells and in mice, their mutation abolishes PER phosphorylation and CLOCK hyperphosphorylation, resulting in PER stabilization, arrhythmic PER abundance and impaired negative feedback process, indicating that PER acts as the CK1 scaffold in circadian feedback mechanism. Surprisingly, the mutant mice exhibit robust short period locomotor activity and other physiological rhythms but low amplitude molecular rhythms. PER-CK1 interaction has two opposing roles in regulating CLOCK-BMAL1 activity. These results indicate that the circadian clock can function independently of PER phosphorylation and abundance rhythms due to another PER-CRY-dependent feedback mechanism and that period length can be uncoupled from PER stability.

Suggested Citation

  • Yang An & Baoshi Yuan & Pancheng Xie & Yue Gu & Zhiwei Liu & Tao Wang & Zhihao Li & Ying Xu & Yi Liu, 2022. "Decoupling PER phosphorylation, stability and rhythmic expression from circadian clock function by abolishing PER-CK1 interaction," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31715-4
    DOI: 10.1038/s41467-022-31715-4
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    1. Rongfeng Huang & Jianghui Chen & Meiyu Zhou & Haoran Xin & Sin Man Lam & Xiaoqing Jiang & Jie Li & Fang Deng & Guanghou Shui & Zhihui Zhang & Min-Dian Li, 2023. "Multi-omics profiling reveals rhythmic liver function shaped by meal timing," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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