NR AOZS
AU Taylor,D.R.; Watt,N.T.; Perera,W.S.S.; Hooper,N.M.
TI On the mechanism of metal-induced endocytosis of the prion protein
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-39
PT Konferenz-Poster
AB The prion protein (PrP), the causative agent of the prion diseases is located in detergent-insoluble lipid rafts at the surface of neuronal cells. Incubation of cells in the presence of copper ions stimulates the endocytosis of PrP. Here we show that disruption of clathrin-mediated endocytosis blocks the copper-induced endocytosis of PrP in a human neuronal cell line whereas cholesterol-binding agents have no effect. Using surface biotinylation and buoyant sucrose density gradient centrifugation in the presence of Triton X-100, we show that on binding copper, PrP is displaced from detergent-insoluble rafts. These data indicate that PrP is normally resident in detergent-insoluble rafts, but on binding Cu2+ moves laterally out of the rafts into the detergent-soluble regions of the plasma membrane, thereby allowing the protein to engage the endocytic machinery of clathrin-coated pits.
AD D.R. Taylor, N.T. Watt, W.S.S. Perera, N.M. Hooper, School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT. UK
SP englisch
PO Deutschland