NR AXOI
AU Heiseke,A.; Lichtenthaler,S.; Vorberg,I.; Schätzl,H.M.; Nunziante,M.
TI A Novel Sorting Nexin (SNX33) Interferes with Prion Infection by Modulation of PrPc Shedding
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC4.1
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB The cellular prion protein (PrPc) is a glycosylphosphatidylinositol (GPI)-anchored protein trafficking in the secretory and endocytic pathway and localized mainly at the plasma membrane. Intramolecular cleavage and shedding of PrPc in the middle, the extreme C-terminal part or within the GPI-anchor, have been implicated in PrP processing. These mechanisms modulate conversion of PrPc into its pathogenic isoform PrPsc, implicated in the pathogenesis and transmission of prion diseases, by reducing the substrate for prion conversion. This provides similarities with the wellcharacterised processing of the Alzheimer precursor protein APP. Sorting nexins are a family of proteins with important functions in protein trafficking. Here, we investigated the role of the newly described sorting-nexin-33 (SNX33) in the trafficking and processing of PrPc. We found that over-expression of SNX33 in neuronal and nonneuronal cell lines results in increased shedding of full-length PrPc from the plasma membrane and modulates the rate of PrPc endocytosis. This was paralleled by reduction of PrPsc formation in persistently infected cells and of de novo infection. Using deletion mutants we demonstrate that production of PrP-fragment N1 is not influenced by SNX33. Our data provide new insights into the cellular mechanisms of PrPc shedding and show how this can affect prion conversion.
AD A. Heiseke, I. Vorberg, H.M. Schätzl, M.Nunziante, Institute of Virology, Technical University of Munich, Germany; S. Lichtenthaler, Adolf-Butenandt-Institute, Germany
SP englisch
PO Schottland