NR AWPV
AU Vella,L.J.; Sharples,R.A.; Lawson,V.A.; Masters,C.L.; Cappai,R.; Hill,A.F.
TI Altered processing of prion proteins packaged into neuronal cell-derived exosomes
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-49
PT Konferenz-Poster
AB The mechanism by which PrPsc, the abnormal isoform of the host-encoded prion protein, PrPc, transfers from the site of peripheral exposure to the lymphoreticular system and subsequently the central nervous system (CNS) is uncertain. In this study we establish that exosomes released from prion infected neuronal and non-neuronal cell lines contain both PrPc and PrPsc. Exosomes from the infected cell lines were efficient initiators of prion propagation in uninfected recipient cells and produced prion disease when inoculated into mice. Moreover, the exosomal associated prion infectivity was transmittable between heterologous cell types in addition to homologous cells, raising the possibility that PrPsc containing exosomes can mediate infectivity transfer between tissues in vivo and suggesting a relationship between prion spread within the CNS and neuronal exosomes. Further investigation has demonstrated that exosomal derived PrP exhibits distinct biochemical properties compared with total intracellular PrP, suggesting altered processing of particular PrP isoforms in this pathway. These data are important for understanding the normal processing of cellular PrP and the dissemination of infectious prions.
AD L.J. Vella, R.A. Sharples, A.F. Hill: Department of Biochemistry & Molecular Biology, Department of Pathology, University of Melbourne, Parkville, Victoria, 3010, Australia, and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, 3052, Australia; V.A. Lawson: Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia; C.L. Masters: Bio21 Molecular Science and Biotechnology Institute, and Department of Pathology, University of Melbourne, Parkville, Victoria, 3052, Australia, and The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia; R. Cappai: Department of Pathology, and Centre for Neuroscience, The University of Melbourne, Parkville, Victoria 3010, Australia, and The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia. E-mail: l.vella@pgrad.unimelb.edu.au
SP englisch
PO Italien