The glycoprotein-processing inhibitors bromoconduritol and N-methyl-1-deoxynojirimycin alter the adhesion phenotype of skeletal myoblasts.
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 beta 1-type integrin(s) as judged by inhibition of adhesion with the beta 1-specific monoclonal antibody JG22. Collagen binding in inhibitor-treated cells remained JG22-sensitive suggesting the inhibitors promote increased activity of a beta 1-type collagen-selective integrin. The effects of BCD, MDJN, and ManDJN on myoblast beta 1-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 myoblast in a proliferative state.
Trudel
G C
GC
Muscle Biochemistry Laboratory, Montréal Neurological Institute, Que., Canada.
Holland
P C
PC
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion / Q000187:drug effects; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism; D053138:Cyclohexenes; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology / Q000187:drug effects*; D010641:Phenotype; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
D053138:Cyclohexenes; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D017485:1-Deoxynojirimycin; C036388:6-bromoconduritol; D007294:Inositol; D003094:Collagen; D005944:Glucosamine; C033424:N-methyldeoxynojirimycin