Anterograde axonal transport of chicken cellular prion protein (PrPc) in vivo requires its N-terminal part.
The cellular isoform of prion protein (PrP(c)) can exist in membrane-bound and secreted forms. Both forms of PrP(c) can be transported by retinal ganglion cell (RGC) axons along the optic nerve in the anterograde direction. In this study we determined which part of chicken PrP(c) is required for its anterograde axonal transport within the optic nerve of embryonic chicken. We intraocularly injected radio-iodinated fragments of recombinant chicken PrP(c) and then examined their anterograde axonal transport from retina into optic tectum. Using gamma-counting and different autoradiographic techniques we quantified anterograde axonal transport of the N-terminal part of chicken PrP(c) (amino acid residues 1-116) in this model system. The transport of the N-terminal part has similar properties as the anterograde transport of full-length chicken PrP(c) (Butowt et al., 2006) described previously (e.g., has similar efficiency, is microtubule-dependent, and is saturable). Moreover, the pattern of ultrastructural distribution of the N-terminal fragment within RGCs is similar to the distribution of full-length PrP(c). The C-terminal fragment of chicken PrP(c) (residues 118-246) and different PrP-derived peptides were not transported. Moreover, PrP(c)-derived peptides were sorted into different endocytotic pathways in neurons, indicating that they cannot substitute for full-length PrP(c) to study its internalization and trafficking. These data indicate that the N-terminal half of chicken PrP(c) contains the necessary information to drive the internalization and subsequent sorting of extracellular PrP(c) in RGCs soma into the anterograde axonal transport pathway.
Butowt
Rafal
R
Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, Nevada, USA.
Davies
Paul
P
Brown
David R
DR
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001370:Axonal Transport / Q000502:physiology*; D002642:Chick Embryo; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008870:Microtubules / Q000502:physiology; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000648:ultrastructure; D011328:Prions / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000648:ultrastructure; D013477:Superior Colliculi / Q000378:metabolism / Q000648:ultrastructure; D014795:Visual Pathways / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
D007456:Iodine Isotopes; D010446:Peptide Fragments; D011328:Prions