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| Subject Categories: Membranes & Transport | Molecular Biology of Disease |
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| The EMBO Journal
(2003) 22, 3591–3601, doi:10.1093/emboj/cdg344 |
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| The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein |
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| Claire Sunyach2, Angela Jen1, Juelin Deng1, Kathleen T. Fitzgerald3, Yveline Frobert4, Jacques Grassi4, Mary W. McCaffrey3 and Roger Morris1 |
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1 Molecular Neurobiology Group, MRC Centre for Developmental Neurobiology, King's College London Guy's Campus, London SEI 1UL, UK 2 Present address: IPMC du CNRS, UPR411, 660 Route des Lucioles, 06560 Valbonne, France 3 Cell and Molecular Biology Laboratory, Biochemistry Dept, UCC Cork, Ireland 4 Service de Pharmacologie et d'Immunologie, CEA/Saclay, 91191 Gif sur Yvette, France To whom correspondence should be addressed Roger Morris, roger.morris@kcl.ac.uk Received 27 May 2002; Revised 6 May 2003; Accepted 20 May 2003. |
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| Abstract |
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| 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. |
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| Keywords: coated pits, endocytosis, GPI, lipid rafts, sphingolipids |
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