A Pathogenic PrP Mutation and Doppel Interfere with Polarized Sorting of the Prion Protein*
A Pathogenic PrP Mutation and Doppel Interfere with Polarized Sorting of the Prion Protein*
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致病性 PrP 突变和 Doppel 干扰朊病毒蛋白的极化分选*
DOI：
10.1074/jbc.c400560200
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发表时间：
2005
影响因子：
4.8
通讯作者：
C. Haass
中科院分区：
文献类型：
--
作者：
Armgard Uelhoff;J. Tatzelt;A. Aguzzi;K. Winklhofer;C. Haass
几种与神经退行性疾病有关的蛋白质，如β-淀粉样前体蛋白、淀粉样蛋白β-肽、β-分泌酶和tau，都进行了选择性极化分类。我们研究了哺乳动物蛋白(PrPC)及其同源多谱勒(DPL)的极化分选。与聚积在根尖表面的DPL不同，PrPC选择性地靶向于Madin-Darby犬肾细胞的基底外侧。广泛的缺失和结构域交换分析表明，PrP(氨基酸113-133)的内部疏水结构域(HD)以基侧排序为主。缺少HD的PrP突变体被顶部排序，而含有PrP HD的DPL嵌合体被定向到基侧膜。此外，HD内致病的PrP错义突变也会导致PrP的异常根尖分类。
Several proteins linked to neurodegenerative diseases, such as the β-amyloid precursor protein, amyloid β-peptide, β-secretase, and tau, undergo selective polarized sorting. We investigated polarized sorting of the mammalian prion protein (PrPC) and its homologue doppel (Dpl). In contrast to Dpl, which accumulates on the apical surface, PrPC is targeted selectively to the basolateral side in Madin-Darby canine kidney cells. An extensive deletion and domain swapping analysis revealed that the internal hydrophobic domain (HD) of PrP (amino acids 113–133) confers basolateral sorting in a dominant manner. PrP mutants lacking the HD are sorted apically, while Dpl chimeras containing the HD of PrP are directed to the basolateral membrane. Furthermore, a pathogenic PrP missense mutation within the HD leads to aberrant apical sorting of PrP as well.
DOI：
10.1073/pnas.91.4.1564
发表时间：
1994-02-15
影响因子：
11.1
作者：
HAASS, C;KOO, EH;SELKOE, DJ
通讯作者：
SELKOE, DJ
影响因子：
56.9
作者：
Hegde, RS;Mastrianni, JA;Lingappa, VR
通讯作者：
Lingappa, VR