Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy.

ABSTRACT: Prion diseases are linked to the accumulation of a misfolded isoform (PrP(Sc)) of prion protein (PrP). Evidence suggests that lysosomes are degradation endpoints and sites of the accumulation of PrP(Sc). We questioned whether lysosomes participate in the early quality control of newly generated misfolded PrP. We found PrP carrying the disease-associated T182A mutation (Mut-PrP) was delivered to lysosomes in a Golgi-independent manner. Time-lapse live cell imaging revealed early formation and uptake of GFP-tagged Mut-PrP aggregates into LysoTracker labeled vesicles. Compared with Wt-PrP, Mut-PrP expression was associated with an elevation in several markers of the autophagy-lysosomal pathway, and it extensively colocalized with the autophagosome-specific marker, LC3B. In autophagy deficient

SUBMITTER: Cortes CJ 

PROVIDER: S-EPMC3877647 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature