NR AOSY
AU Geißen,M.; Mella,H.; Saalmüller,A.; Oelschlegel,A.M.; Pfaff,E.; Schätzl,H.M.; Groschup,M.H.
TI Insertion of a Heptapeptide Sequence at 33 Consecutive Positions of Prion Protein: Impact on Glycosylation, Convertibility and Cellular Trafficking
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-53
PT Konferenz-Poster
AB It is still not clear which structural elements of the prion protein are involved and crucially important for the PrP conversion process. To systematically address this question a set of 33 insertion mutants was generated. A kemptide sequence was introduced at evenly spaced sites through out the whole sequence of murine 3F4-tagged PrP. These mutants were characterised in regard to their expression and convertibility in non-infected and in scrapie infected murine neuronal cells. It was intriguing to see by fluorescence activated cell sorting (FACS) and western-blot analysis that the heptapeptide insertion led to differences in cellular processing in some mutant proteins while others were not affected. Similarly, the convertibility of particular insertion mutants was well conserved while most mutations in the PrP core part blocked the intrinsic convertibility. In some cases this led even to a transdominant inhibition of the endogenous perpetuation of the scrapie infection in the cells itself. The here presented results stress the involvement of the core part of PrP for the conversion process. Understanding these molecular mechanisms will allow to design new strategies to prevent or inhibit prion infections.
AD M. Geißen, H. Mella, A. Oelschlegel, M.H. Groschup, Federal Research Centre for Virus Diseases of Animals, Insel Riems, Germany; A. Saalmüller, E. Pfaff, Federal Research Centre for Virus Diseases of Animals, Tübingen, Germany; H.M. Schätzl, Technische Universität München, München, Germany
SP englisch
PO Deutschland