Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10956788 | Molecular and Cellular Neuroscience | 2005 | 13 Pages |
Abstract
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.
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Authors
Birkir Thor Bragason, Astridur Palsdottir,