Lysine Interacts with Frizzled7 to Activate ß-Catenin in Satellite Cell-Participated Skeletal Muscle Growth.

ABSTRACT

This work provided an interesting finding of lysine (Lys) control on skeletal muscle growth besides protein synthesis. According to the isobaric tag for relative and absolute quantitation and molecular docking analyses, we found both in in vivo skeletal muscle and in vitro muscle satellite cells (MuSCs) that the frizzled7 (FZD7) expression level was positively correlated with Lys levels and this was consistent with the activation of the Wnt/ß-catenin pathway. On the other hand, FZD7 inhibition suppressed the Lys-rescued Wnt/ß-catenin pathway, FZD7 knockdown caused cell proliferation, and Wnt/ß-catenin pathway restrictions could not be compensated for by Lys or Wnt3a. Furthermore, the combination between Lys and recombinant pig frizzled7 (rpFZD7) protein was confirmed by isothermal titration calorimetry. This finding displayed concrete evidence that Lys is not only a molecular block of protein synthesis but is also a ligand for FZD7 to activate ß-catenin to stimulate MuSCs in promoting skeletal muscle growth.