NR AOHW
AU Walmsley,A.R.; Zeng,F.; Hooper,N.M.
TI The N-terminal region of the prion protein ectodomain contains a lipid raft targeting determinant
QU The Journal of Biological Chemistry 2003 Sep 26; 278(39): 37241-8
PT journal article
AB The association of the prion protein (PrP) with sphingolipid- and cholesterol-rich lipid rafts is instrumental in the pathogenesis of the neurodegenerative prion diseases. Although the glycosylphosphatidylinositol (GPI) anchor is an exoplasmic determinant of raft association, PrP remained raft-associated in human neuronal cells even when the GPI anchor was deleted or substituted for a transmembrane anchor indicating that the ectodomain contains a raft localization signal. The raft association of transmembrane-anchored PrP occurred independently of Cu(II) binding as it failed to be abolished by either deletion of the octapeptide repeat region (residues 51-90) or treatment of cells with a Cu(II) chelator. Raft association of transmembrane-anchored PrP was only abolished by the deletion of the N-terminal region (residues 23-90) of the ectodomain. This region was sufficient to confer raft localization when fused to the N terminus of a non-raft transmembrane-anchored protein and suppressed the clathrin-coated pit localization signal in the cytoplasmic domain of the amyloid precursor protein. These data indicate that the N-terminal region of PrP acts as a cellular raft targeting determinant and that residues 23-90 of PrP represent the first proteinaceous raft targeting signal within the ectodomain of a GPI-anchored protein.
MH Amyloid beta-Protein Precursor/metabolism; Cell Line, Tumor; Cytoplasm/metabolism; Glycosylphosphatidylinositols/physiology; Human; Membrane Microdomains/*metabolism; Peptide Fragments/physiology; Prions/*chemistry/physiology; Support, Non-U.S. Gov't
AD School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.
SP englisch
PO USA