title: The cellular isoform of the prion protein, PrPc, is associated with caveolae in mouse neuroblastoma (N2a) cells.
abstract: A major component of the infectious particle causing spongiform encephalopathies or prion diseases is an aberrant isoform (PrPSc) of a glycosyl-phosphatidylinositol (GPI)-anchored cell surface protein, PrPC. The cellular processes involved in the formation of PrPSc are unclear but involve the internalization of PrPC prior to conversion. Here, we demonstrate that PrPC is associated with caveolin, a structural protein component of caveolae. We show that PrPC and caveolin share similar detergent characteristics and copurify in linear sucrose gradients. PrPC was protected from proteinase K digestion in the caveolin fraction but solubilizing the caveolae prior to proteinase K digestion rendered PrPC susceptible to proteinase K digestion. Our results indicate a physical association between PrPC and caveolin in N2a cells. The implication of these results in relation to prion biogenesis is discussed.
authors.affiliation: Department of Zoology, University College Dublin, Belfield, Ireland.
authors.forename: J H
authors.initials: JH
authors.lastname: Harmey
authors.forename: D
authors.initials: D
authors.lastname: Doyle
authors.forename: V
authors.initials: V
authors.lastname: Brown
authors.forename: M S
authors.initials: MS
authors.lastname: Rogers
mesh_terms: D000818:Animals; D051242:Caveolin 1; D022461:Caveolins; D002460:Cell Line; D002462:Cell Membrane / Q000648:ultrastructure; D002499:Centrifugation, Density Gradient; D003902:Detergents; D005455:Fluorescent Antibody Technique; D017261:Glycosylphosphatidylinositols / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis* / Q000302:isolation & purification; D051379:Mice; D009447:Neuroblastoma / Q000648:ultrastructure*; D018621:PrPC Proteins / Q000032:analysis* / Q000302:isolation & purification; D012995:Solubility; D014407:Tumor Cells, Cultured
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D003902:Detergents; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D018621:PrPC Proteins