Gow A, Lazzarini R A
Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Nat Genet. 1996 Aug;13(4):422-8. doi: 10.1038/ng0896-422.
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.
佩利措伊斯-梅茨巴赫病（PMD）是一种与蛋白脂质蛋白基因（PLP）相关的脑白质营养不良症。我们基于两种PLP基因产物（PLP和DM20）的蛋白质运输，报道了区分两种疾病亚型（经典型和先天性）的细胞基础。经典型PMD突变与转染的COS-7细胞内质网中PLP的积累相关，而同源的DM20则穿过分泌途径到达细胞表面。另一方面，先天性PMD突变导致COS-7细胞内质网中突变型PLP和DM20蛋白均积累，两种异构体很少运输到细胞表面。此外，我们表明具有运输能力的突变型DM20有助于同源PLP的运输，因此可能影响疾病严重程度。
