NR ATIB
AU Vella,L.J.; Sharples,R.A.; Masters,C.L.; Cappai,R.; Hill,A.F.
TI Proteomic investigation into the propagation and spread of infectious prions in non-neuronal cells
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-33
PT Konferenz-Poster
AB Prion diseases are transmissible neurodegenerative disorders which include Creutzfeldt-Jakob disease in humans, scrapie in sheep and bovine spongiform encephalopathy in cattle. According to the protein-only hypothesis, an abnormal isoform of the host encoded prion protein (PrPc), referred to as PrPsc, is the sole or major component of the infectious agent. Discrepancies between PrPsc and its relationship to prion infectivity and neurotoxicity suggest that alternative forms of PrP, distinct from infectious PrP and / or unidentified cellular factors, are necessary for the acquisition of infectivity and may be involved in the mechanisms of prion toxicity. Using a mouse-adapted strain of human prions we have developed cell models using mouse GT1 cells and mouse PrP expressing RK13 cells which propagate infectious prions in vitro, providing a means to investigate cellular factors involved in prion propagation. Previous studies have demonstrated that cells can release infectious prions associated with exosomes. Consistent with this, we have isolated exosomes from the culture medium of our infected cells and demonstrate the presence of PrPsc. When isolated from the cell media, exosomes from our infected cells can transmit infection to non-infected cells, suggesting cellular co-factors necessary for the generation of infectivity are contained within the exosomes. Due to the unique protein composition of exosomes we are using a proteomic approach to examine the protein profile of expressed proteins of infected versus non-infected exosomes to identify cellular factors implicated in the propagation and spread of infectious prions.
AD L.J.Vella, R.A.Sharples, A.F.Hill, Department of Biochemistry & Molecular Biology, Bio21 Institute, University of Melbourne, Australia; L.J.Vella, R.A.Sharples, C.L.Masters, R.Cappai, A.F.Hill, Department of Pathology, University of Melbourne, Australia; R.Cappai, Centre for Neuroscience, University of Melbourne, Australia; C.L.Masters, R.Cappai, Mental Health Research Institute of Victoria, University of Melbourne, Australia
SP englisch
PO Deutschland