The low-density lipoprotein receptor-related protein 1 (LRP1) mediates the endocytosis of the cellular prion protein

David R Taylor , Nigel M Hooper (1)

1 Institute of Molecular and Cellular Biology

The cellular prion protein (PrP C}) is located at the surface of neuronal cells in detergent-insoluble lipid rafts, yet is internalised 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 siRNA of particular low-density lipoprotein family members, in combination with immunofluorescence microscopy and surface biotinylation assays, we show that the transmembrane low-density lipoprotein receptor-related protein 1 (LRP1) 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}.

Mots clés: Life Sciences

David R Taylor, Nigel M Hooper. The low-density lipoprotein receptor-related protein 1 (LRP1) mediates the endocytosis of the cellular prion protein. Biochemical Journal, 2006, 402 (1), pp.17-23. ⟨10.1042/BJ20061736⟩. ⟨hal-00478699⟩