The glycoprotein-processing inhibitors bromoconduritol and N-methyl-1-deoxynojirimycin alter the adhesion phenotype of skeletal myoblasts

Abstract

Treatment of chick myoblasts with the glucosidase inhibitors bromoconduritol (BCD) or N-methyl-1-deoxynojirimycin (MDJN), but not the mannosidase I inhibitor 1-deoxymannojirimycin (ManDJN), decreased their rate of adhesion to fibronectin and laminin and increased their rate of adhesion to collagen types I and IV. The adhesion of chick myoblasts to fibronectin, collagen type IV, and laminin was predominantly mediated by β1-type integrin(s) as judged by inhibition of adhesion with the β1-specific monoclonal antibody JG22. Collagen binding in inhibitor-treated cells remained JG22-sensitive suggesting the inhibitors promote increased activity of a β1-type collagen-selective integrin. The effects of BCD, MDJN, and ManDJN on myoblast β1-integrin detectable at the myoblast cell surface with JG22 antibody correlated well with their effects on adhesion to fibronectin and laminin, and paralleled the previously reported effects of these agents on myogenesis. Interaction of integrin with the extracellular matrix appears to be required for myoblast terminal differentiation. We found that Mn2+ ions increased the adhesion of myoblasts to extracellular matrix proteins and antagonized the effect of BCD and MDJN on myoblast differentiation, supporting a role for cell–matrix interactions in myogenesis. Inhibition of myogenesis by BCD or MDJN was not reversed by growth under low serum conditions, suggesting these agents do not act by maintaining myoblasts in a proliferative state.Key words: myoblast, myogenesis, integrin, cell adhesion, glycoprotein processing.