| http://purl.uniprot.org/citations/16254249 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16254249 | http://www.w3.org/2000/01/rdf-schema#comment | "The cellular prion protein (PrP(C)) is essential for the pathogenesis and transmission of prion diseases. Although PrP(C) is known to be located in detergent-insoluble lipid rafts at the surface of neuronal cells, the mechanism of its internalisation is unclear, with both raft/caveolae-based and clathrin-mediated processes being proposed. We have investigated the mechanism of copper-induced internalisation of PrP(C) in neuronal cells by immunofluorescence microscopy, surface biotinylation assays and buoyant sucrose density gradient centrifugation in the presence of Triton X-100. Clathrin-mediated endocytosis was selectively blocked with tyrphostin A23, which disrupts the interaction between tyrosine motifs in the cytosolic domains of integral membrane proteins and the adaptor complex AP2, and a dominant-negative mutant of the adaptor protein AP180. Both these agents inhibited the copper-induced endocytosis of PrP(C). Copper caused PrP(C) to move laterally out of detergent-insoluble lipid rafts into detergent-soluble regions of the plasma membrane. Using mutants of PrP(C) that lack either the octapeptide repeats or the N-terminal polybasic region, and a construct with a transmembrane anchor, we show that copper binding to the octapeptide repeats promotes dissociation of PrP(C) from lipid rafts, whereas the N-terminal polybasic region mediates its interaction with a transmembrane adaptor protein that engages the clathrin endocytic machinery. Our results provide an experimental basis for reconciling the apparently contradictory observations that the prion protein undergoes clathrin-dependent endocytosis despite being localised in lipid rafts. In addition, we have been able to assign distinct functions in the endocytic process to separate regions of the protein."xsd:string |
| http://purl.uniprot.org/citations/16254249 | http://purl.org/dc/terms/identifier | "doi:10.1242/jcs.02627"xsd:string |
| http://purl.uniprot.org/citations/16254249 | http://purl.uniprot.org/core/author | "Hooper N.M."xsd:string |
| http://purl.uniprot.org/citations/16254249 | http://purl.uniprot.org/core/author | "Taylor D.R."xsd:string |
| http://purl.uniprot.org/citations/16254249 | http://purl.uniprot.org/core/author | "Perera W.S."xsd:string |
| http://purl.uniprot.org/citations/16254249 | http://purl.uniprot.org/core/author | "Watt N.T."xsd:string |
| http://purl.uniprot.org/citations/16254249 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/16254249 | http://purl.uniprot.org/core/name | "J Cell Sci"xsd:string |
| http://purl.uniprot.org/citations/16254249 | http://purl.uniprot.org/core/pages | "5141-5153"xsd:string |
| http://purl.uniprot.org/citations/16254249 | http://purl.uniprot.org/core/title | "Assigning functions to distinct regions of the N-terminus of the prion protein that are involved in its copper-stimulated, clathrin-dependent endocytosis."xsd:string |
| http://purl.uniprot.org/citations/16254249 | http://purl.uniprot.org/core/volume | "118"xsd:string |
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