FKRP-dependent glycosylation of fibronectin regulates muscle pathology in muscular dystrophy

A. J. Wood, C. H. Lin, M. Li, K. Nishtala, S. Alaei, F. Rossello, C. Sonntag, L. Hersey, L. B. Miles, C. Krisp, S. Dudczig, A. J. Fulcher, S. Gibertini, P. J. Conroy, A. Siegel, Marina Mora, P. Jusuf, N. H. Packer, P. D. Currie*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)
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    The muscular dystrophies encompass a broad range of pathologies with varied clinical outcomes. In the case of patients carrying defects in fukutin-related protein (FKRP), these diverse pathologies arise from mutations within the same gene. This is surprising as FKRP is a glycosyltransferase, whose only identified function is to transfer ribitol-5-phosphate to α-dystroglycan (α-DG). Although this modification is critical for extracellular matrix attachment, α-DG’s glycosylation status relates poorly to disease severity, suggesting the existence of unidentified FKRP targets. Here we reveal that FKRP directs sialylation of fibronectin, a process essential for collagen recruitment to the muscle basement membrane. Thus, our results reveal that FKRP simultaneously regulates the two major muscle-ECM linkages essential for fibre survival, and establishes a new disease axis for the muscular dystrophies.

    Original languageEnglish
    Article number2951
    Pages (from-to)1-12
    Number of pages12
    JournalNature Communications
    Issue number1
    Publication statusPublished - 19 May 2021

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    Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


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