IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35547-0.html
   My bibliography  Save this article

Muscle 4EBP1 activation modifies the structure and function of the neuromuscular junction in mice

Author

Listed:
  • Seok-Ting J. Ang

    (National University of Singapore
    National University of Singapore)

  • Elisa M. Crombie

    (National University of Singapore)

  • Han Dong

    (National University of Singapore)

  • Kuan-Ting Tan

    (National University of Singapore)

  • Adriel Hernando

    (National University of Singapore)

  • Dejie Yu

    (National University of Singapore
    National University of Singapore
    National University of Singapore)

  • Stuart Adamson

    (Buck Institute for Research on Aging)

  • Seonyoung Kim

    (National University of Singapore)

  • Dominic J. Withers

    (Medical Research Council Clinical Council London Institute of Medical Sciences (LMS)
    Imperial College London)

  • Hua Huang

    (National University of Singapore
    National University of Singapore
    National University of Singapore)

  • Shih-Yin Tsai

    (National University of Singapore
    National University of Singapore)

Abstract

Dysregulation of mTOR complex 1 (mTORC1) activity drives neuromuscular junction (NMJ) structural instability during aging; however, downstream targets mediating this effect have not been elucidated. Here, we investigate the roles of two mTORC1 phosphorylation targets for mRNA translation, ribosome protein S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), in regulating NMJ structural instability induced by aging and sustained mTORC1 activation. While myofiber-specific deletion of S6k1 has no effect on NMJ structural integrity, 4EBP1 activation in murine muscle induces drastic morphological remodeling of the NMJ with enhancement of synaptic transmission. Mechanistically, structural modification of the NMJ is attributed to increased satellite cell activation and enhanced post-synaptic acetylcholine receptor (AChR) turnover upon 4EBP1 activation. Considering that loss of post-synaptic myonuclei and reduced NMJ turnover are features of aging, targeting 4EBP1 activation could induce NMJ renewal by expanding the pool of post-synaptic myonuclei as an alternative intervention to mitigate sarcopenia.

Suggested Citation

  • Seok-Ting J. Ang & Elisa M. Crombie & Han Dong & Kuan-Ting Tan & Adriel Hernando & Dejie Yu & Stuart Adamson & Seonyoung Kim & Dominic J. Withers & Hua Huang & Shih-Yin Tsai, 2022. "Muscle 4EBP1 activation modifies the structure and function of the neuromuscular junction in mice," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35547-0
    DOI: 10.1038/s41467-022-35547-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35547-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-35547-0?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. Perrine Castets & Nathalie Rion & Marine Théodore & Denis Falcetta & Shuo Lin & Markus Reischl & Franziska Wild & Laurent Guérard & Christopher Eickhorst & Marielle Brockhoff & Maitea Guridi & Chikwen, 2019. "mTORC1 and PKB/Akt control the muscle response to denervation by regulating autophagy and HDAC4," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    2. Daniel J. Ham & Anastasiya Börsch & Shuo Lin & Marco Thürkauf & Martin Weihrauch & Judith R. Reinhard & Julien Delezie & Fabienne Battilana & Xueyong Wang & Marco S. Kaiser & Maitea Guridi & Michael S, 2020. "The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia," Nature Communications, Nature, vol. 11(1), pages 1-21, December.
    Full references (including those not matched with items on IDEAS)

    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. Jean-Philippe Leduc-Gaudet & Anais Franco-Romero & Marina Cefis & Alaa Moamer & Felipe E. Broering & Giulia Milan & Roberta Sartori & Tomer Jordi Chaffer & Maude Dulac & Vincent Marcangeli & Dominique, 2023. "MYTHO is a novel regulator of skeletal muscle autophagy and integrity," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Daniel J. Ham & Anastasiya Börsch & Kathrin Chojnowska & Shuo Lin & Aurel B. Leuchtmann & Alexander S. Ham & Marco Thürkauf & Julien Delezie & Regula Furrer & Dominik Burri & Michael Sinnreich & Chris, 2022. "Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Anirban Roy & Ashok Kumar, 2022. "Supraphysiological activation of TAK1 promotes skeletal muscle growth and mitigates neurogenic atrophy," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    4. Betz, Ulrich A.K. & Arora, Loukik & Assal, Reem A. & Azevedo, Hatylas & Baldwin, Jeremy & Becker, Michael S. & Bostock, Stefan & Cheng, Vinton & Egle, Tobias & Ferrari, Nicola & Schneider-Futschik, El, 2023. "Game changers in science and technology - now and beyond," Technological Forecasting and Social Change, Elsevier, vol. 193(C).
    5. Marco Thürkauf & Shuo Lin & Filippo Oliveri & Dirk Grimm & Randall J. Platt & Markus A. Rüegg, 2023. "Fast, multiplexable and efficient somatic gene deletions in adult mouse skeletal muscle fibers using AAV-CRISPR/Cas9," Nature Communications, Nature, vol. 14(1), pages 1-16, 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_s41467-022-35547-0. 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.