title: Heterogeneity and regulation of cellular prion protein glycoforms in neuronal cell lines.
abstract: The normal cellular prion protein is a small sialoglycoprotein highly expressed in neurons, the physiological function of which is largely unknown. Due to extensive N-glycosylations with a wide range of oligosaccharides, the prion protein displays a complex glycosylation pattern that could be of relevance for its function. The cellular prion protein patterns in adult mouse and rat brain, and in neuronal cell lines, appeared highly heterogeneous, as distinct levels and glycoforms of cellular prion protein were revealed by immunoblotting of corresponding samples. Amongst neuronal cell lines, mouse N2a neuroblastoma cells expressed low levels of endogenous prion protein. Mouse hypothalamic GT1-7 cells and rat pheochromocytoma PC-12 cells expressed highly glycosylated forms of cellular prion protein that were found neither in adult mouse and rat brain, nor in mouse brain during development. In contrast, rat B104 neuroblastoma cells abundantly expressed N-glycosylated cellular prion protein forms similar to those observed in mouse and rat brain. In all these cell lines, the prion protein was normally exported to and expressed at the outer cell membrane. Our results suggest that B104 cells may represent an appropriate cell model to investigate the physiological role of cellular prion protein in further detail as they highly express the normal 'brain-like' cellular prion protein glycoforms. In addition, we observed that the various prion glycoforms in B104 cells were tightly regulated both as a function of cell density and during neuronal differentiation, implying a potential role of cellular prion protein in cell-cell interactions and differentiation.
authors.affiliation: Signalisation et Différenciation Cellulaires dans les Systèmes Nerveux et Musculaire, U440 INSERM/UPMC, Institut du Fer à Moulin, 17 rue du Fer à Moulin, 75005 Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Monnet
authors.forename: Véronique
authors.initials: V
authors.lastname: Marthiens
authors.forename: Hervé
authors.initials: H
authors.lastname: Enslen
authors.forename: Yveline
authors.initials: Y
authors.lastname: Frobert
authors.forename: André
authors.initials: A
authors.lastname: Sobel
authors.forename: René Marc
authors.initials: RM
authors.lastname: Mège
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006031:Glycosylation; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D051381:Rats
chemical_list: D011328:Prions