IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms11534.html
   My bibliography  Save this article

ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ribitol phosphate onto α-dystroglycan

Author

Listed:
  • Isabelle Gerin

    (WELBIO and de Duve Institute, Biological Chemistry, Université Catholique de Louvain)

  • Benoît Ury

    (WELBIO and de Duve Institute, Biological Chemistry, Université Catholique de Louvain)

  • Isabelle Breloy

    (Institute for Biochemistry II, Medical Faculty, University of Cologne)

  • Céline Bouchet-Seraphin

    (AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Biochimie Métabolique et Cellulaire)

  • Jennifer Bolsée

    (WELBIO and de Duve Institute, Biological Chemistry, Université Catholique de Louvain)

  • Mathias Halbout

    (WELBIO and de Duve Institute, Biological Chemistry, Université Catholique de Louvain)

  • Julie Graff

    (WELBIO and de Duve Institute, Biological Chemistry, Université Catholique de Louvain)

  • Didier Vertommen

    (WELBIO and de Duve Institute, Biological Chemistry, Université Catholique de Louvain)

  • Giulio G. Muccioli

    (Louvain Drug Research Institute, Université Catholique de Louvain)

  • Nathalie Seta

    (AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Biochimie Métabolique et Cellulaire)

  • Jean-Marie Cuisset

    (Hôpital Roger-Salengro, Service de neuropédiatrie, Centre de Référence des Maladies Neuromusculaires, CHRU)

  • Ivana Dabaj

    (AP-HP, Hôpital R Poincaré, Service de pédiatrie)

  • Susana Quijano-Roy

    (AP-HP, Hôpital R Poincaré, Service de pédiatrie
    Centre de Référence des Maladies Neuromusculaires
    Université de Versailles-St Quentin)

  • Ammi Grahn

    (WELBIO and de Duve Institute, Biological Chemistry, Université Catholique de Louvain
    Present address: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, SE 413 45 Göteborg, Sweden.)

  • Emile Van Schaftingen

    (WELBIO and de Duve Institute, Biological Chemistry, Université Catholique de Louvain)

  • Guido T. Bommer

    (WELBIO and de Duve Institute, Biological Chemistry, Université Catholique de Louvain)

Abstract

Mutations in genes required for the glycosylation of α-dystroglycan lead to muscle and brain diseases known as dystroglycanopathies. However, the precise structure and biogenesis of the assembled glycan are not completely understood. Here we report that three enzymes mutated in dystroglycanopathies can collaborate to attach ribitol phosphate onto α-dystroglycan. Specifically, we demonstrate that isoprenoid synthase domain-containing protein (ISPD) synthesizes CDP-ribitol, present in muscle, and that both recombinant fukutin (FKTN) and fukutin-related protein (FKRP) can transfer a ribitol phosphate group from CDP-ribitol to α-dystroglycan. We also show that ISPD and FKTN are essential for the incorporation of ribitol into α-dystroglycan in HEK293 cells. Glycosylation of α-dystroglycan in fibroblasts from patients with hypomorphic ISPD mutations is reduced. We observe that in some cases glycosylation can be partially restored by addition of ribitol to the culture medium, suggesting that dietary supplementation with ribitol should be evaluated as a therapy for patients with ISPD mutations.

Suggested Citation

  • Isabelle Gerin & Benoît Ury & Isabelle Breloy & Céline Bouchet-Seraphin & Jennifer Bolsée & Mathias Halbout & Julie Graff & Didier Vertommen & Giulio G. Muccioli & Nathalie Seta & Jean-Marie Cuisset &, 2016. "ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ribitol phosphate onto α-dystroglycan," Nature Communications, Nature, vol. 7(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11534
    DOI: 10.1038/ncomms11534
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms11534
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms11534?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
    ---><---

    Citations

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


    Cited by:

    1. M. Osman Sheikh & Chantelle J. Capicciotti & Lin Liu & Jeremy Praissman & Dahai Ding & Daniel G. Mead & Melinda A. Brindley & Tobias Willer & Kevin P. Campbell & Kelley W. Moremen & Lance Wells & Geer, 2022. "Cell surface glycan engineering reveals that matriglycan alone can recapitulate dystroglycan binding and function," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Hideki Tokuoka & Rieko Imae & Hitomi Nakashima & Hiroshi Manya & Chiaki Masuda & Shunsuke Hoshino & Kazuhiro Kobayashi & Dirk J. Lefeber & Riki Matsumoto & Takashi Okada & Tamao Endo & Motoi Kanagawa , 2022. "CDP-ribitol prodrug treatment ameliorates ISPD-deficient muscular dystrophy mouse model," Nature Communications, Nature, vol. 13(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:7:y:2016:i:1:d:10.1038_ncomms11534. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.