A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic reticululm
A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic reticululm
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DOI：
10.1091/mbc.12.4.881
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发表时间：
2001-04-01
影响因子：
3.3
通讯作者：
Harris, DA
中科院分区：
文献类型：
--
作者：
Stewart, RS;Drisaldi, B;Harris, DA
虽然有相当多的证据表明PrPSc是PrP蛋白的感染性形式，但最近有研究表明，一种称为(PrP)-Pr-CTM的跨膜变异体是PrP相关神经变性的直接原因。我们在这里报道，使用专门与(PrP)-Pr-CTM拓扑合成的PrP的突变形式，(PrP)-Pr-CTM保留在内质网中，并被蛋白酶体降解。我们还证明了(PrP)-Pr-CTM含有一个未切割的N-末端信号肽和一个C-末端糖脂锚。这些结果提供了对内质网中膜蛋白合成过程中控制膜蛋白拓扑结构的一般机制的洞察，也提示了(PrP)-Pr-CTM可能导致疾病的细胞途径。
Although there is considerable evidence that PrPSc is the infectious form of the prion protein, it has recently been proposed that a transmembrane variant called (PrP)-Pr-Ctm is the direct cause of prion-associated neurodegeneration. We report here, using a mutant form of PrP that is synthesized exclusively with the (PrP)-Pr-Ctm topology, that (PrP)-Pr-Ctm is retained in the endoplasmic reticulum and is degraded by the proteasome. We also demonstrate that (PrP)-Pr-Ctm contains an uncleaved, N-terminal signal peptide as well as a C-terminal glycolipid anchor. These results provide insight into general mechanisms that control the topology of membrane proteins during their synthesis in the endoplasmic reticulum, and they also suggest possible cellular pathways by which (PrP)-Pr-Ctm may cause disease.