The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein

C Sunyach; A Jen; J Deng; K T Fitzgerald; Y Frobert; J Grassi; M W McCaffrey; R Morris

doi:10.1093/emboj/cdg344

The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein

C Sunyach
, A Jen
, J Deng
, K T Fitzgerald
, Y Frobert
, J Grassi
, M W McCaffrey
, R Morris

Chemistry

Research output: Contribution to journal › Article › peer-review

256 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	3591 - 3601
Number of pages	11
Journal	EMBO Journal
Volume	22
Issue number	14
DOIs	https://doi.org/10.1093/emboj/cdg344
Publication status	Published - 15 Jul 2003

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abstract = "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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AU - Sunyach, C

AU - Jen, A

AU - Deng, J

AU - Fitzgerald, K T

AU - Frobert, Y

AU - Grassi, J

AU - McCaffrey, M W

AU - Morris, R

PY - 2003/7/15

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AB - 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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DO - 10.1093/emboj/cdg344

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ER -

The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein

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