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

Caroline Brun (1) , Olivier Monestier (1) , Sébastien Legardinier (1) , Abderrahman A. Maftah (1) , Véronique V. Blanquet (1)

1 UMR GMA - Unité de Génétique Moléculaire Animale

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. [br/] Methods: We describe herein the site-directed mutagenesis of single N-glycosylation sites and combinations of them in 4 mutants of murine GASP-1. [br/] 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. [br/] 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.

Mots clés: gasp-1; gdf8; glycosylation; secretion; myogenesis

Domaines: Sciences du Vivant [q-bio]

Caroline Brun, Olivier Monestier, Sébastien Legardinier, Abderrahman A. Maftah, Véronique V. Blanquet. Murine GASP-1 N-Glycosylation is not Essential for its Activity on C2C12 Myogenic Cells but Alters its Secretion. Cellular Physiology and Biochemistry, 2012, 30 (3), pp.791-804. ⟨10.1159/000341458⟩. ⟨hal-01211973⟩