Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy

Figure 6

Ultrastructural markers of autophagy with Mut-PrP expression. Transmission electron micrographs of transiently transfected COS-7 cells ((a)–(d)) and stably transfected N2a cells ((e)–(j)). TEM of COS-7 cells expressing Wt (a) or Mut- ((b)–(d)) PrP for 24 h. Normal appearing ultrastructure present in cells expressing Wt-PrP (a), and abnormal membranes characteristic of isolation membranes ((b), asterisk), double membrane autophagosomes (c), and myelinoid (multilamellar) bodies (d) were evident in the majority of cell sections sampled from Mut-PrP expressing cells. (e)–(j) Mouse neuroblastoma N2a cells stably expressing Wt-PrP ((e)–(f)) or Mut-PrP ((g)–(j)). Mut-PrP expressing cells displayed an accumulation of multivesicular bodies and autophagy-related structures consistent with late stage autophagosomes and/or autolysosomes. These structures were largely absent in cells expressing Wt-PrP.