NR ATGZ
AU Miesbauer,M.; Bamme,T.; Riemer,C.; Oidtmann,B.; Winklhofer,K.F.; Baier,M.; Tatzelt,J.
TI Biochemical characterization of prion proteins from zebra fish
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-05
PT Konferenz-Poster
AB A hallmark of prion diseases in mammals is a conformational transition of the cellular prion protein (PrPc) into a pathogenic isoform termed PrPsc. The biogenesis of PrPc plays a central role in the pathogenesis of prion diseases; transgenic mice devoid of PrPc neither replicate infectious prions nor succumb to prion diseases. PrPc is characterized by extensive post-translational modifications. The C-terminal domain harbors a glycosylphosphatidylinositol (GPI) anchor, which targets PrPc to the outer leaflet of the plasma membrane, and two N-linked glycans of complex structure. Studies in cell culture and transgenic animals indicated that the formation of PrPsc occurs after fully maturated PrPc has reached the plasma membrane or is re-internalized for degradation. Most recently, genes of PrP-related proteins have been identified in fish. While there is only little sequence homology between fish and mammalian PrP, it appears that characteristic features of mammalian PrPc, like repeats in the N-terminal domain, an internal hydrophobic domain and a disulfide bridge in the C-terminal domain, are conserved. In addition, it was predicted that fish prion proteins contain signal sequences for targeting to the endoplasmic reticulum and for GPI anchor attachment and harbor consensus sites for N-linked glycosylation. Experimental evidence for the post-translational modifications, however, are still missing. To analyze their biogenesis, maturation and cellular localization, we have cloned different PrP-related proteins from zebrafish into mammalian expression vectors. We will present a comprehensive biochemical analysis of these PrP-related proteins in neuronal cells.
AD Margit Miesbauer, Konstanze F. Winklhofer, Jörg Tatzelt, Max-Planck-Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany; Theresa Bamme, Constanze Riemer, Michael Baier, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany; Birgit Oidtmann, CEFAS Weymouth Laboratory, Molecular Genetics, Barrack Road, The Nothe, Weymouth, Dorset DT48UB, UK
SP englisch
PO Deutschland