IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43826-7.html
   My bibliography  Save this article

Excess PrPC inhibits muscle cell differentiation via miRNA-enhanced liquid–liquid phase separation implicated in myopathy

Author

Listed:
  • Jing Tao

    (Wuhan University)

  • Yanping Zeng

    (Renmin Hospital of Wuhan University)

  • Bin Dai

    (Wuhan University)

  • Yin Liu

    (Renmin Hospital of Wuhan University)

  • Xiaohan Pan

    (State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences)

  • Li-Qiang Wang

    (Wuhan University
    Wuhan University Shenzhen Research Institute)

  • Jie Chen

    (Wuhan University)

  • Yu Zhou

    (Wuhan University)

  • Zuneng Lu

    (Renmin Hospital of Wuhan University)

  • Liwei Xie

    (State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences)

  • Yi Liang

    (Wuhan University
    Wuhan University Shenzhen Research Institute)

Abstract

The cellular prion protein (PrPC) is required for skeletal muscle function. Here, we report that a higher level of PrPC accumulates in the cytoplasm of the skeletal muscle of six myopathy patients compared to controls. PrPC inhibits skeletal muscle cell autophagy, and blocks myoblast differentiation. PrPC selectively binds to a subset of miRNAs during myoblast differentiation, and the colocalization of PrPC and miR-214-3p was observed in the skeletal muscle of six myopathy patients with excessive PrPC. We demonstrate that PrPC is overexpressed in skeletal muscle cells under pathological conditions, inhibits muscle cell differentiation by physically interacting with a subset of miRNAs, and selectively recruits these miRNAs into its phase-separated condensate in living myoblasts, which in turn enhances liquid–liquid phase separation of PrPC, promotes pathological aggregation of PrP, and results in the inhibition of autophagy-related protein 5-dependent autophagy and muscle bundle formation in myopathy patients characterized by incomplete muscle regeneration.

Suggested Citation

  • Jing Tao & Yanping Zeng & Bin Dai & Yin Liu & Xiaohan Pan & Li-Qiang Wang & Jie Chen & Yu Zhou & Zuneng Lu & Liwei Xie & Yi Liang, 2023. "Excess PrPC inhibits muscle cell differentiation via miRNA-enhanced liquid–liquid phase separation implicated in myopathy," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43826-7
    DOI: 10.1038/s41467-023-43826-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43826-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43826-7?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. Giorgia Giacomazzi & Bryan Holvoet & Sander Trenson & Ellen Caluwé & Bojana Kravic & Hanne Grosemans & Álvaro Cortés-Calabuig & Christophe M. Deroose & Danny Huylebroeck & Said Hashemolhosseini & Stef, 2017. "MicroRNAs promote skeletal muscle differentiation of mesodermal iPSC-derived progenitors," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    2. Michele Vendruscolo & Monika Fuxreiter, 2022. "Protein condensation diseases: therapeutic opportunities," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Forrest Hoyt & Heidi G. Standke & Efrosini Artikis & Cindi L. Schwartz & Bryan Hansen & Kunpeng Li & Andrew G. Hughson & Matteo Manca & Olivia R. Thomas & Gregory J. Raymond & Brent Race & Gerald S. B, 2022. "Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    4. Szymon W. Manka & Wenjuan Zhang & Adam Wenborn & Jemma Betts & Susan Joiner & Helen R. Saibil & John Collinge & Jonathan D. F. Wadsworth, 2022. "2.7 Å cryo-EM structure of ex vivo RML prion fibrils," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Aishwarya Agarwal & Lisha Arora & Sandeep K. Rai & Anamika Avni & Samrat Mukhopadhyay, 2022. "Spatiotemporal modulations in heterotypic condensates of prion and α-synuclein control phase transitions and amyloid conversion," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Shunsuke F. Shimobayashi & Pierre Ronceray & David W. Sanders & Mikko P. Haataja & Clifford P. Brangwynne, 2021. "Nucleation landscape of biomolecular condensates," Nature, Nature, vol. 599(7885), pages 503-506, November.
    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. Ashish Joshi & Anuja Walimbe & Anamika Avni & Sandeep K. Rai & Lisha Arora & Snehasis Sarkar & Samrat Mukhopadhyay, 2023. "Single-molecule FRET unmasks structural subpopulations and crucial molecular events during FUS low-complexity domain phase separation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Glenn C. Telling, 2022. "The shape of things to come: structural insights into how prion proteins encipher heritable information," Nature Communications, Nature, vol. 13(1), pages 1-3, December.
    3. Juan Manuel Valverde & Geronimo Dubra & Michael Phillips & Austin Haider & Carlos Elena-Real & Aurélie Fournet & Emile Alghoul & Dhanvantri Chahar & Nuria Andrés-Sanchez & Matteo Paloni & Pau Bernadó , 2023. "A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    4. Forrest Hoyt & Heidi G. Standke & Efrosini Artikis & Cindi L. Schwartz & Bryan Hansen & Kunpeng Li & Andrew G. Hughson & Matteo Manca & Olivia R. Thomas & Gregory J. Raymond & Brent Race & Gerald S. B, 2022. "Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    5. Mónika Gönczi & João M. C. Teixeira & Susana Barrera-Vilarmau & Laura Mediani & Francesco Antoniani & Tamás Milán Nagy & Krisztina Fehér & Zsolt Ráduly & Viktor Ambrus & József Tőzsér & Endre Barta & , 2023. "Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Juan Du & Keunhwa Kim & Meng Chen, 2024. "Distinguishing individual photobodies using Oligopaints reveals thermo-sensitive and -insensitive phytochrome B condensation at distinct subnuclear locations," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    7. Darren B. McAffee & Mark K. O’Dair & Jenny J. Lin & Shalini T. Low-Nam & Kiera B. Wilhelm & Sungi Kim & Shumpei Morita & Jay T. Groves, 2022. "Discrete LAT condensates encode antigen information from single pMHC:TCR binding events," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    8. Agustín Mangiarotti & Macarena Siri & Nicky W. Tam & Ziliang Zhao & Leonel Malacrida & Rumiana Dimova, 2023. "Biomolecular condensates modulate membrane lipid packing and hydration," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    9. Jingru Fang & Guillaume Castillon & Sebastien Phan & Sara McArdle & Chitra Hariharan & Aiyana Adams & Mark H. Ellisman & Ashok A. Deniz & Erica Ollmann Saphire, 2023. "Spatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Samuel T. Dada & Zenon Toprakcioglu & Mariana P. Cali & Alexander Röntgen & Maarten C. Hardenberg & Owen M. Morris & Lena K. Mrugalla & Tuomas P. J. Knowles & Michele Vendruscolo, 2024. "Pharmacological inhibition of α-synuclein aggregation within liquid condensates," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Agustín Mangiarotti & Nannan Chen & Ziliang Zhao & Reinhard Lipowsky & Rumiana Dimova, 2023. "Wetting and complex remodeling of membranes by biomolecular condensates," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Chenyang Lan & Juhyeong Kim & Svenja Ulferts & Fernando Aprile-Garcia & Sophie Weyrauch & Abhinaya Anandamurugan & Robert Grosse & Ritwick Sawarkar & Aleks Reinhardt & Thorsten Hugel, 2023. "Quantitative real-time in-cell imaging reveals heterogeneous clusters of proteins prior to condensation," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    13. Steen W. B. Bender & Marcus W. Dreisler & Min Zhang & Jacob Kæstel-Hansen & Nikos S. Hatzakis, 2024. "SEMORE: SEgmentation and MORphological fingErprinting by machine learning automates super-resolution data analysis," Nature Communications, Nature, vol. 15(1), pages 1-13, 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:14:y:2023:i:1:d:10.1038_s41467-023-43826-7. 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.