Park, Y., Kim, W., Kim, A.Y., Choi, H.J., Choi, J.K., Park, N., Koh, E.K., Seo, J., Koh, Y.H. (2011). Normal prion protein in Drosophila enhances the toxicity of pathogenic polyglutamine proteins and alters susceptibility to oxidative and autophagy signaling modulators.  Biochem. Biophys. Res. Commun. 404(2): 638--645.

FBrf0212784

Research paper

To investigate the in vivo functions of normal prion protein (PrP) in Drosophila, we utilized characterized transgenic flies expressing ³(F)⁴-tagged mouse PrP (Mo-PrP³(F)⁴). The neurotoxicity of pathogenic Machado-Joseph Disease (MJD) glutamine (Q) 78 and 127Q proteins were enhanced by the co-expression of Mo-PrP³(F)⁴in the fly eyes, while the eyes of controls flies and flies expressing Mo-PrP³(F)⁴) alone or together with MJD-Q27 or 20Q proteins did not show any defect. Susceptibilities to H₂O₂, paraquat, and Dithiothreitol (DTT) were altered in Mo-PrP³(F)⁴ flies. In addition, Mo-PrP³(F)⁴ flies were significantly more susceptible to the perturbation of autophagy signaling by an autophagy inhibitor, 3-methyladenine (3-MA), and inducer, LiCl. Taken together, our data suggest that Mo-PrP³(F)⁴ may enhance the neurotoxicity of pathogenic Poly-Q proteins by perturbing oxidative and autophagy signaling.