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A truncated Wnt7a retains full biological activity in skeletal muscle

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  • Julia von Maltzahn

    (Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute
    Present address: Leibniz Institute for Age Research, Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07445 Jena, Germany)

  • Radoslav Zinoviev

    (Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute)

  • Natasha C. Chang

    (Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute)

  • C. Florian Bentzinger

    (Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute)

  • Michael A. Rudnicki

    (Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute
    University of Ottawa)

Abstract

Wnt signaling has essential roles during embryonic development and tissue homoeostasis. Wnt proteins are post-translationally modified and the attachment of a palmitate moiety at two conserved residues is believed to be a prerequisite for the secretion and function of Wnt proteins. Here we demonstrate that a mammalian Wnt protein can be fully functional without palmitoylation. We generate a truncated Wnt7a variant, consisting of the C-terminal 137 amino acids lacking the conserved palmitoylation sites and show that it retains full biological activity in skeletal muscle. This includes binding to and signaling through its receptor Fzd7 to stimulate symmetric expansion of satellite stem cells by activating the planar-cell polarity pathway and inducing myofibre hypertrophy by signaling through the AKT/mTOR pathway. Furthermore, this truncated Wnt7a shows enhanced secretion and dispersion compared with the full-length protein. Together, these findings open important new avenues for the development of Wnt7a as a treatment for muscle-wasting diseases and have broad implications for the therapeutic use of Wnts as biologics.

Suggested Citation

  • Julia von Maltzahn & Radoslav Zinoviev & Natasha C. Chang & C. Florian Bentzinger & Michael A. Rudnicki, 2013. "A truncated Wnt7a retains full biological activity in skeletal muscle," Nature Communications, Nature, vol. 4(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3869
    DOI: 10.1038/ncomms3869
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