Anterograde axonal transport of the exogenous cellular isoform of prion protein in the chick visual system

The cellular isoform of endogenous, newly synthesized prion protein (PrPc) can be transported by axons in the anterograde direction. To determine whether a mechanism exists for secreted PrPc to be internalized and then axonally transported, we analyzed internalization and anterograde axonal transport of radiolabeled recombinant PrPc after its intraocular injection in chick embryos. Internalization and axonal transport of exogenous PrPc to the midbrain by retinal ganglion cells (RGCs) is efficient, saturable and likely receptor-mediated. Ultrastructural quantitative localization of radiolabeled PrPc within RGC soma showed significant labeling of vesicular/endosomal compartments and much less labeling present over the Golgi apparatus and lysosomes, which indicates slow degradation of exogenous PrPc in this system. These data show that a mechanism exists to internalize a secreted form of PrPc and then to axonally transport such PrPc in an anterograde direction. This may provide an additional, novel mechanism for prion protein to spread among neurons.