title: Interaction of PrP with NRAGE, a protein involved in neuronal apoptosis.
abstract: Prion diseases involve the conversion of the endogenous prion protein, PrP(C), into a disease-associated form PrP(Sc). Reports show that a subset of PrP(C) is subject to degradation in the cytosol by the ubiquitin-proteasome system. Some studies show that cytosolic PrP(C) is neuroprotective, while others show that it is neurotoxic. Here, we report that cytosolic PrP(C) constructs interact with a pro-apoptotic protein, NRAGE (neurotrophin receptor interacting MAGE homolog). This novel interaction was identified in a yeast two-hybrid screen using PrP(C) as bait and confirmed by an in vitro binding assay and co-immunoprecipitations. Endogenous NRAGE accumulated in perinuclear aggregates following proteasome inhibition, and recombinant NRAGE and PrP(C)-EGFP co-localized in aggresomes after proteasome inhibition. Finally, co-expression of NRAGE and cytosolic PrP(C) affected mitochondrial membrane potential in neuroblastoma cells. Our results suggest that interaction of cytosolic PrP and NRAGE could affect neuronal viability.
authors.affiliation: Institute for Experimental Pathology, Keldur, University of Iceland, Reykjavik 112, Iceland.
authors.forename: Birkir Thor
authors.initials: BT
authors.lastname: Bragason
authors.forename: Astridur
authors.initials: A
authors.lastname: Palsdottir
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D019556:COS Cells; D002470:Cell Survival / Q000502:physiology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005260:Female; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D046911:Macromolecular Substances / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D016716:PC12 Cells; D018621:PrPC Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism* / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D051381:Rats
chemical_list: D046911:Macromolecular Substances; C486541:Maged1 protein, mouse; D009363:Neoplasm Proteins; D018621:PrPC Proteins; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex