Journal article

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

AJ Wood, CH Lin, M Li, K Nishtala, S Alaei, F Rossello, C Sonntag, L Hersey, LB Miles, C Krisp, S Dudczig, AJ Fulcher, S Gibertini, PJ Conroy, A Siegel, M Mora, P Jusuf, NH Packer, PD Currie



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 ..

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by Australian Research Council Linkage

Awarded by LIEF Grant

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (NHMRC) (PDC, NP: APP1127741, PDC: APP1136567, APP3151883). Australian Research Council Linkage (PDC: LP120100281) in collaboration with Sigma-Aldrich and LIEF Grant (LE150100110). The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. We acknowledge J Callaghan, I Harper, Monash Micro Imaging Facility, J Clark and A Costin, Monash Electron Microscopy Facility, L Kautto, Australian Proteomic Analysis Facility, W Moore, J Hilton and J Manneken, Aquacore core staff, Australian Regenerative Medicine Institute and Monash University Micromon sequencing facility for technical support. We also thank G Lynch and M Anderson for paper critiques.