Peer-Reviewed Journal Details
Mandatory Fields
Sunyach, C,Jen, A,Deng, J,Fitzgerald, KT,Frobert, Y,Grassi, J,McCaffrey, MW,Morris, R;
2003
January
The Embo Journal
The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein
Validated
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Optional Fields
coated pits endocytosis GPI lipid rafts sphingolipids SCRAPIE-ASSOCIATED FORM CLATHRIN-COATED PITS CELL-SURFACE SUBCELLULAR TRAFFICKING DEPENDENT RETENTION NEUROBLASTOMA-CELLS ENDOCYTIC PATHWAY NEURONAL SURFACE RESISTANT STATE CULTURED-CELLS
22
3591
3601
The mode of internalization of glycosylphosphatidylinositol-anchored proteins, lacking any cytoplasmic domain by which to engage adaptors to recruit them into coated pits, is problematical; that of prion protein in particular is of interest since its cellular trafficking appears to play an essential role in its pathogenic conversion. Here we demonstrate, in primary cultured neurons and the N2a neural cell line, that prion protein is rapidly and constitutively endocytosed. While still on the cell surface, prion protein leaves lipid 'raft' domains to enter non-raft membrane, from which it enters coated pits. The N-terminal domain (residues 23-107) of prion protein is sufficient to direct internalization, an activity dependent upon its initial basic residues (NH2-KKRPKP). The effect of this changing membrane environment upon the susceptibility of prion protein to pathogenic conversion is discussed.
Grant Details