NR AWIG
AU Krammer,C.; Diemer,C.; Scheibel,T.; Schätzl,H.M.; Vorberg,I.
TI Spontaneous aggregate formation in mammalian cells expressing chimeric yeast sup35p/ mouse prion proteins
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 PA-31
PT Konferenz-Poster
AB A hallmark of prion diseases is the conversion of the cellular prion protein PrPc into misfolded PrPsc, most probably the etiologic agent. A prion-like phenomenon has also been reported for the yeast, in which the translation termination factor Sup35p can adopt an altered conformation that is transmissible to daughter cells. Striking parallels make the well characterized yeast prions an ideal model to study principal mechanisms of prion formation. To investigate the importance of prion domains for prion aggregate formation fusion proteins of yeast Sup35p and murine PrP were expressed in mammalian cells. In yeast, prion formation of Sup35p or its prion forming domain NM is dependent on the existence of several identified co-factors. In mammalian cells, cytosolic NM was unable to aggregate, suggesting that NM is either unable to spontaneously aggregate in mammalian cells per se or that important co-factors needed for its conformational transition might be missing. However, fusion of NM to amino acid residues 90-230 of PrP (NM-PrP) rendered cytosolic NM capable of spontaneously forming aggregates that differed dramatically in size and frequency from the very small aggregates observed with control cytosolic PrP. Aggregate formation was also observed with N-PrP, arguing that the yeast M domain was dispensable for aggregation. Immunofluorescence analysis revealed that the chimera did not display typical characteristics of aggresomes. In conclusion, fusion of Sup35p prion domains to PrP leads to the spontaneous generation of chimeric aggregates with unique characteristics. Any potential amyloidogenic nature of Sup35p-PrP aggregates will be elucidated in future experiments.
AD C. Krammer, C. Diemer, H.M. Schätzl, I. Vorberg: Institute of Virology, Technical University of Munich (TUM), Trogerstraße 30, D-81675 Munich, Germany; T. Scheibel: Department of Chemistry, Chair of Biotechnology, Technical University of Munich (TUM), Lichtenbergstraße 4, D-85747 Garching, Germany
SP englisch
PO Italien