NR ASWE
AU Bragason,B.T.; Palsdottir,A.
TI Interaction of PrP with NRAGE, a protein involved in neuronal apoptosis
QU Molecular and Cellular Neurosciences 2005 Jun; 29(2): 232-44
PT journal article
AB Prion diseases involve the conversion of the endogenous prion protein, PrPc, into a disease-associated form PrPsc. Reports show that a subset of PrPc is subject to degradation in the cytosol by the ubiquitin-proteasome system. Some studies show that cytosolic PrPc is neuroprotective, while others show that it is neurotoxic. Here, we report that cytosolic PrPc 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 PrPc 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 PrPc-EGFP co-localized in aggresomes after proteasome inhibition. Finally, co-expression of NRAGE and cytosolic PrPc affected mitochondrial membrane potential in neuroblastoma cells. Our results suggest that interaction of cytosolic PrP and NRAGE could affect neuronal viability.
MH Animals; Apoptosis/*physiology; Brain/*metabolism/physiopathology; COS Cells; Cell Survival/physiology; Cercopithecus aethiops; Disease Models, Animal; Female; Inclusion Bodies/metabolism/pathology; Macromolecular Substances/metabolism; Membrane Potentials/physiology; Mice; Mice, Inbred BALB C; Mitochondria/metabolism; Neoplasm Proteins/*metabolism; Nerve Degeneration/*metabolism/physiopathology; PC12 Cells; PrPc Proteins/*metabolism; Prion Diseases/*metabolism/physiopathology; Proteasome Endopeptidase Complex/antagonists & inhibitors/metabolism; Rats; Research Support, Non-U.S. Gov't
AD Institute for Experimental Pathology, Keldur, University of Iceland, Reykjavik 112, Iceland.
SP englisch
PO USA