The low-density lipoprotein receptor-related protein 1 (LRP1) mediates the endocytosis of the cellular prion protein.
PrP(C) (cellular prion protein) is located at the surface of neuronal cells in detergent-insoluble lipid rafts, yet is internalized by clathrin-dependent endocytosis. As PrP(C) is glycosyl-phosphatidylinositol-anchored, it requires a transmembrane adaptor protein to connect it to the clathrin endocytosis machinery. Using receptor-associated protein and small interfering RNA against particular LDL (low-density lipoprotein) family members, in combination with immunofluorescence microscopy and surface biotinylation assays, we show that the transmembrane LRP1 (LDL receptor-related protein 1) is required for the Cu(2+)-mediated endocytosis of PrP(C) in neuronal cells. We show also that another LRP1 ligand that can cause neurodegenerative disease, the Alzheimer's amyloid precursor protein, does not modulate the endocytosis of PrP(C).
Taylor
David R
DR
Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK.
Hooper
Nigel M
NM
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D002966:Clathrin / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D026563:LDL-Receptor Related Protein-Associated Protein / Q000378:metabolism; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D002966:Clathrin; D026563:LDL-Receptor Related Protein-Associated Protein; C434476:LRP1B protein, human; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D018621:PrPC Proteins; D034741:RNA, Small Interfering; D011973:Receptors, LDL; D003300:Copper