Role of glycoproteins in neuronal differentiation. Inhibition of neurite outgrowth and the major cell surface glycoprotein of murine neuroblastoma cells by a purified tunicamycin homologue.
Mouse neuroblastoma cells in culture can be induced to differentiate morphologically by serum deprivation or by dibutyryl cyclic AMP (db-cAMP), e.g. they appear flattened, adhere more firmly to the culture substratum and extend long neuritic processes, and thus represent a widely used model system for neuronal cells. This differentiation is accompanied by modulation of cell surface components, such as the induction of a high molecular weight (HMW) glycoprotein (200 kD). We have studied the role of glycoproteins in the process of neuronal differentiation, using a purified homologue of the antibiotic tunicamycin (Al-tunicamycin) and neuroblastoma N115 cells grown in culture. Al-tunicamycin markedly inhibited (up to 60-75%) the incorporation of radioactively labelled sugars into cellular proteins of differentiating neuroblastoma cells. Concomitantly, the cells altered their morphology, they became rounded and less adhesive and retracted their neurites. Changes in the appearance, glycosylation and electrophoretic mobility of several cellular and secreted glycoproteins were observed, when cells were incubated in the presence of Al-tunicamycin. The most striking effect of Al-tunicamycin on the composition of cellular glycoproteins was the marked reduction in appearance of the 200 kD glycoprotein. The findings suggest that glycoproteins and in particular the neuron-specific 200 kD glycoprotein, are related to morphological differentiation processes, mainly to cellular adhesion and neurite outgrowth.
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D005944:Glucosamine / Q000031:analogs & derivatives*; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010455:Peptides / Q000032:analysis; D014415:Tunicamycin / Q000031:analogs & derivatives* / Q000494:pharmacology
D003470:Culture Media; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D014415:Tunicamycin; C039973:tunicamycin A1; D005944:Glucosamine