Protein O-GlcNAcylation is required for fibroblast growth factor signaling in Drosophila

Daniel Mariappa, Kathrin Sauert, Karina Marino, Daniel Turnock, Ryan Webster, Daan M. F. van Aalten, Michael A. J. Ferguson, H. Arno J. Muller (Lead / Corresponding author)

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    18 Citations (Scopus)

    Abstract

    Glycosylation is essential for growth factor signaling through N-glycosylation of ligands and receptors and the biosynthesis of proteoglycans as co-receptors. Here, we show that protein O-GlcNAcylation is crucial for fibroblast growth factor (FGF) signaling in Drosophila. We found that nesthocker (nst) encodes a phosphoacetylglucosamine mutase and that nst mutant embryos exhibited low amounts of intracellular uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc), which disrupted protein O-GlcNAcylation. Nst was required for mitogen-activated protein kinase (MAPK) signaling downstream of FGF but not MAPK signaling activated by epidermal growth factor. nst was dispensable for the function of the FGF ligands and the FGF receptor's extracellular domain but was essential in the signal-receiving cells downstream of the FGF receptor. We identified the adaptor protein Downstream of FGF receptor (Dof), which interacts with the FGF receptor, as the relevant target for O-GlcNAcylation in the FGF pathway, suggesting that protein O-GlcNAcylation of the activated receptor complex is essential for FGF signal transduction.

    Original languageEnglish
    Article numberra89
    Pages (from-to)-
    Number of pages8
    JournalScience Signaling
    Volume4
    Issue number204
    DOIs
    Publication statusPublished - 20 Dec 2011

    Keywords

    • GLCNAC transferase
    • Cell migration
    • X-chromosome
    • Gene
    • Embryos
    • Complex
    • Morphogenesis
    • Glycosylation
    • Viability
    • Tracheal

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