HETEROLOGOUS PRP MOLECULES INTERFERE WITH ACCUMULATION OF PROTEASE-RESISTANT PRP IN SCRAPIE-INFECTED MURINE NEUROBLASTOMA-CELLS
HETEROLOGOUS PRP MOLECULES INTERFERE WITH ACCUMULATION OF PROTEASE-RESISTANT PRP IN SCRAPIE-INFECTED MURINE NEUROBLASTOMA-CELLS
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DOI：
10.1128/jvi.68.8.4873-4878.1994
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发表时间：
1994-08-01
影响因子：
5.4
通讯作者：
CHESEBRO, B
中科院分区：
文献类型：
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作者：
PRIOLA, SA;CAUGHEY, B;CHESEBRO, B
宿主细胞蛋白PrP中的突变与传染性海绵状脑病的疾病有关。持续感染小鼠瘙痒病的小鼠神经母细胞瘤细胞积聚了抗蛋白酶PrP(PrP-res)，PrP-RES是一种异常形式的PrP，与传染性海绵状脑病的疾病相关。这些细胞提供了一个受控系统，在其中研究在PrP-RES形成中重要的分子相互作用。我们在小鼠瘙痒病感染的小鼠神经母细胞瘤细胞中表达了重组PrP分子，并检测了这些异源PrP基因对PrP-RES形成和积累的影响。结果表明，异源PrP分子的表达与内源PrP分子相差只有一个氨基酸，可以深刻地干扰PrP-RES的整体积累。这些数据表明，同源PrP分子之间的精确相互作用在PrP-RES的积累中很重要，而异种PrP分子可以阻止这些相互作用。
Mutations within a host cellular protein, PrP, have been associated with disease in the transmissible spongiform encephalopathies. Murine neuroblastoma cells persistently infected with mouse scrapie accumulate protease-resistant PrP (PrP-res), the abnormal form of PrP associated with disease in the transmissible spongiform encephalopathies. These cells provide a controlled system in which to study the molecular interactions which are important in the formation of PrP-res. We have expressed recombinant PrP molecules in mouse scrapie-infected murine neuroblastoma cells and assayed the effect of these heterologous PrP genes on the formation and accumulation of PrP-res. The results demonstrate that expression of heterologous PrP molecules which differ from the endogenous PrP by as little as one amino acid can profoundly interfere with the overall accumulation of PrP-res. The data suggest that precise interactions between homologous PrP molecules are important in PrP-res accumulation and that heterologous PrP molecules can block these interactions.