A cellular mechanism governing the severity of Pelizaeus-Merzbacher disease
A cellular mechanism governing the severity of Pelizaeus-Merzbacher disease
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DOI：
10.1038/ng0896-422
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发表时间：
1996-08-01
期刊：
影响因子：
30.8
通讯作者：
Lazzarini, RA
中科院分区：
文献类型：
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作者：
Gow, A;Lazzarini, RA
Pelizaeus-Merzbacher病（PMD）是一种与蛋白脂蛋白基因（PLP）相关的白质营养不良。我们报告了基于两种PLP基因产物（PLP和DM20）的蛋白质转运的两种疾病亚型（经典和先天性）之间的细胞基础区分。经典的PMD突变与转染的COS-7细胞内质网中PLP的积累有关，而同源DM20则通过分泌途径到达细胞表面。另一方面，先天性PMD突变导致突变的PLP和DM20蛋白在COS-7细胞的内质膜中积累，很少有异构体被转运到细胞表面。此外，我们发现具有运输能力的突变DM20s促进同源PLPs的运输，因此可能影响疾病的严重程度。
Pelizaeus-Merzbacher disease (PMD) is a leukodystrophy linked to the proteolipid protein gene (PLP). We report a cellular basis for the distinction between two disease subtypes, classical and connatal, based on protein trafficking of the two PLP gene products (PLP and DM20). Classical PMD mutations correlate with accumulation of PLP in the ER of transfected COS-7 cells while the cognate DM20 traverses the secretory pathway to the cell surface. On the other hand, connatal PMD mutations lead to the accumulation of both mutant PLP and DM20 proteins in the ER of COS-7 cells with little of either isoform transported to the cell surface. Moreover, we show that transport-competent mutant DM20s facilitate trafficking of cognate PLPs and hence may influence disease severity.