Uptake and Neuritic Transport of Scrapie Prion Protein Coincident with Infection of Neuronal Cells
Open Access
- 25 May 2005
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 25 (21) , 5207-5216
- https://doi.org/10.1523/jneurosci.0653-05.2005
Abstract
Invasion of the nervous system and neuronal spread of infection are critical, but poorly understood, steps in the pathogenesis of transmissible spongiform encephalopathies or prion diseases. To characterize pathways for the uptake and intraneuronal trafficking of infectious, protease-resistant prion protein (PrP-res), fluorescent-labeled PrP-res was used to infect a neuronally derived murine cell line (SN56) and adult hamster cortical neurons in primary culture. Concurrent with the establishment of persistent scrapie infection, SN56 cells internalized PrP-res aggregates into vesicles positive for markers for late endosomes and/or lysosomes but not synaptic, early endocytic, or raft-derived vesicles. Internalized PrP-res was then transported along neurites to points of contact with other cells. Similar trafficking was observed with dextran, Alzheimer's Aβ1-42 fibrils and noninfectious recombinant PrP fibrils, suggesting that PrP-res is internalized by a relatively nonspecific pinocytosis or transcytosis mechanism. Hamster cortical neurons were also capable of internalizing and disseminating exogenous PrP-res. Similar trafficking of exogenous PrP-res by cortical neurons cultured from the brains of PrP knock-out mice showed that uptake and neuritic transport did not require the presence of endogenous cellular PrP. These experiments visualize and characterize the initial steps associated with prion infection and transport within neuronal cells.Keywords
This publication has 57 references indexed in Scilit:
- Acute Formation of Protease-resistant Prion Protein Does Not Always Lead to Persistent Scrapie Infection in VitroJournal of Biological Chemistry, 2004
- Effects of Cholesterol Depletion and Increased Lipid Unsaturation on the Properties of Endocytic MembranesJournal of Biological Chemistry, 2004
- Stimulation of PrPC Retrograde Transport toward the Endoplasmic Reticulum Increases Accumulation of PrPSc in Prion-infected CellsJournal of Biological Chemistry, 2002
- Endocytic Intermediates Involved with the Intracellular Trafficking of a Fluorescent Cellular Prion ProteinJournal of Biological Chemistry, 2002
- Retrograde Transport of Transmissible Mink Encephalopathy within Descending Motor TractsJournal of Virology, 2002
- Binding of prion protein to lipid membranes and implications for prion conversionJournal of Molecular Biology, 2002
- Trafficking of green fluorescent protein tagged‐vesicular acetylcholine transporter to varicosities in a cholinergic cell lineJournal of Neurochemistry, 2001
- Fluid‐phase marker transport in rat liver: Free‐flow electrophoresis separates distinct endosome subpopulationsElectrophoresis, 1998
- A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoformJournal of Molecular Biology, 1997
- Acidification of endocytic compartments and the intracellular pathways of ligands and receptorsJournal of Cellular Biochemistry, 1984