The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein
The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein
复制标题
DOI：
10.1093/emboj/cdg344
复制
发表时间：
2003-07-15
期刊：
影响因子：
11.4
通讯作者：
Morris, R
中科院分区：
文献类型：
--
作者：
Sunyach, C;Jen, A;Morris, R
糖基磷脂酰肌醇锚定蛋白的内化模式是有问题的，缺乏任何细胞质结构域来接合接头以将它们招募到包被的凹坑中；朊病毒蛋白尤其令人感兴趣，因为其细胞运输似乎在其致病性转化中发挥重要作用。在这里，我们证明，在原代培养的神经元和 N2a 神经细胞系中，朊病毒蛋白被快速且组成性地内吞。当朊病毒蛋白仍在细胞表面时，它会离开脂质“筏”结构域进入非筏膜，并从非筏膜进入有涂层的凹坑。朊病毒蛋白的 N 端结构域（残基 23-107）足以指导内化，其活性取决于其初始碱性残基 (NH2-KKRPKP)。讨论了这种变化的膜环境对朊病毒蛋白致病性转化敏感性的影响。
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.