Murine GASP-1 N-Glycosylation is not Essential for its Activity on C2C12 Myogenic Cells but Alters its Secretion

作者：Brun Caroline; Monestier Olivier; Legardinier Sebastien; Maftah Abderrahman; Blanquet Veronique^*

来源：Cellular Physiology and Biochemistry, 2012, 30(3): 791-804.

DOI：10.1159/000341458

• GASP-1
• GDF8
• Glycosylation
• Secretion
• Myogenesis

Background/Aims: Growth and differentiation factor-associated serum protein-1 (GASP-1) is a secreted protein known to be capable of binding and inhibiting the activity of several TGF-beta family members, including myostatin. The present study was designed to characterize murine GASP-1 post-translational modifications and to determine their influence on the biological activity of GASP-1. Methods: We describe herein the site-directed mutagenesis of single N-glycosylation sites and combinations of them in 4 mutants of murine GASP-1. Results: In vitro and in vivo analysis revealed that GASP-1 is a glycoprotein containing 2 N-glycans and several mucin-type O-glycans. Treatments by the recombinant murine GASP-1 protein enhance C2C12 proliferation and differentiation by inhibition of the myostatin pathway. The loss of N-glycans leads to a decrease in protein secretion rate but does not affect its ability to activate myogenesis. Conclusion: Analysis of structure-function relationships of murine GASP-1 provides insights into the involvement of the carbohydrate moiety of mGASP-1 on its biological activity.

• 出版日期2012