IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31715-4.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31715-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-31715-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Ying Xu & Quasar S. Padiath & Robert E. Shapiro & Christopher R. Jones & Susan C. Wu & Noriko Saigoh & Kazumasa Saigoh & Louis J. Ptáček & Ying-Hui Fu, 2005. "Functional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome," Nature, Nature, vol. 434(7033), pages 640-644, March.
    2. Daisuke Ono & Sato Honma & Ken-ichi Honma, 2013. "Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus," Nature Communications, Nature, vol. 4(1), pages 1-11, June.
    3. Weiman Xing & Luca Busino & Thomas R. Hinds & Samuel T. Marionni & Nabiha H. Saifee & Matthew F. Bush & Michele Pagano & Ning Zheng, 2013. "SCFFBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket," Nature, Nature, vol. 496(7443), pages 64-68, April.
    4. Gijsbertus T. J. van der Horst & Manja Muijtjens & Kumiko Kobayashi & Riya Takano & Shin-ichiro Kanno & Masashi Takao & Jan de Wit & Anton Verkerk & Andre P. M. Eker & Dik van Leenen & Ruud Buijs & Di, 1999. "Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms," Nature, Nature, vol. 398(6728), pages 627-630, April.
    5. Linda Lauinger & Axel Diernfellner & Sebastian Falk & Michael Brunner, 2014. "The RNA helicase FRH is an ATP-dependent regulator of CK1a in the circadian clock of Neurospora crassa," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Seref Gul & Yasemin Kubra Akyel & Zeynep Melis Gul & Safak Isin & Onur Ozcan & Tuba Korkmaz & Saba Selvi & Ibrahim Danis & Ozgecan Savlug Ipek & Fatih Aygenli & Ali Cihan Taskin & Büşra Aytül Akarlar , 2022. "Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Zhiwei Zhao & Craig Dent & Huafeng Liang & Junqing Lv & Guandong Shang & Yawen Liu & Fan Feng & Fei Wang & Junhong Pang & Xu Li & Libang Ma & Bing Li & Sridevi Sureshkumar & Jia-Wei Wang & Sureshkumar, 2022. "CRY2 interacts with CIS1 to regulate thermosensory flowering via FLM alternative splicing," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Henson, Michael A., 2013. "Multicellular models of intercellular synchronization in circadian neural networks," Chaos, Solitons & Fractals, Elsevier, vol. 50(C), pages 48-64.
    4. 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.
    5. Sahar Foroutannejad & Lydia L. Good & Changfan Lin & Zachariah I. Carter & Mahlet G. Tadesse & Aaron L. Lucius & Brian R. Crane & Rodrigo A. Maillard, 2023. "The cofactor-dependent folding mechanism of Drosophila cryptochrome revealed by single-molecule pulling experiments," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Tomasz Pałka & Przemysław Pajor & Anna Katarzyna Tyka & Wanda Pilch & Agata Cebula & Aneta Teległów & Marek Strzała & Marcin Maciejczyk, 2021. "Time-of-Day Effects on Anaerobic Power and Concentration of Selected Hormones in Blind Men," IJERPH, MDPI, vol. 18(17), pages 1-12, September.
    7. Yasuko O. Abe & Hikari Yoshitane & Dae Wook Kim & Satoshi Kawakami & Michinori Koebis & Kazuki Nakao & Atsu Aiba & Jae Kyoung Kim & Yoshitaka Fukada, 2022. "Rhythmic transcription of Bmal1 stabilizes the circadian timekeeping system in mammals," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31715-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.