The importance of N-linked glycoproteins and dolichyl phosphate synthesis for fusion of L6 myoblasts.
Myoblasts fuse to form multinucleated myotubes, one of the early steps in the formation of multinucleated muscle fiber. The fusion reaction is accompanied by biochemical differentiation resulting in the expression of a variety of enzyme activities and macromolecules, particularly creatine phosphokinase. The fusing myoblast is thus an excellent system for use in studies on the molecular basis of cellular recognition. This report focuses on the role played by glycoproteins in this process. It was found that alteration of cell-surface glycoproteins, using oligosaccharide-processing inhibitors that interfered with the synthesis of the high-mannose type of N-linked oligosaccharide, resulted in the inhibition of both the fusion reaction and biochemical differentiation as determined by measurement of creatine phosphokinase. Ketoconazole, compactin, and lovastatin, which affect dolichol and cholesterol biosynthesis, were also potent fusion inhibitors. These observations, coupled with earlier studies on the characterization of fusion-defective myoblast cell lines defective in glycoprotein biosynthesis, point to the importance of surface glycoproteins in cellular recognition in L6 myoblasts.
Jamieson
J C
JC
Department of Chemistry, University of Manitoba, Winnipeg, Canada.
Wayne
S
S
Belo
R S
RS
Wright
J A
JA
Spearman
M A
MA
D017485:1-Deoxynojirimycin / Q000494:pharmacology; D000818:Animals; D002240:Carbohydrate Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion / Q000187:drug effects; D003402:Creatine Kinase / Q000032:analysis; D004288:Dolichol Phosphates / Q000378:metabolism*; D006023:Glycoproteins / Q000502:physiology*; D007212:Indolizines / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000502:physiology*; D009132:Muscles / Q000166:cytology*; D009844:Oligosaccharides / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D017026:Swainsonine / Q000494:pharmacology; D054836:Indolizidines
D017485:1-Deoxynojirimycin; D003402:Creatine Kinase; D004288:Dolichol Phosphates; D006023:Glycoproteins; D007212:Indolizines; D007654:Ketoconazole; D008148:Lovastatin; D009124:Muscle Proteins; D009844:Oligosaccharides; D017026:Swainsonine; C028306:dolichol monophosphate; C012258:mevastatin; C037806:castanospermine; D054836:Indolizidines