Copper and zinc cause delivery of the prion protein from the plasma membrane to a subset of early endosomes and the Golgi
Copper and zinc cause delivery of the prion protein from the plasma membrane to a subset of early endosomes and the Golgi
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DOI：
10.1046/j.1471-4159.2003.01996.x
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发表时间：
2003-10-01
影响因子：
4.7
通讯作者：
Harris, DA
中科院分区：
文献类型：
--
作者：
Brown, LR;Harris, DA
朊病毒蛋白（PrPC）是一种细胞膜糖蛋白，其构象转化为PrPSc是朊病毒传播的中心分子事件。然而，PrPC的生理功能仍然不确定。PrPC以低微摩尔亲和力结合铜离子的发现，加上其他几个观察结果，导致了该蛋白质在铜稳态中发挥作用的建议。使用生物化学技术，我们以前已经表明，铜离子快速和可逆地刺激细胞表面的PrPC的内吞作用。在这份报告中，我们采用免疫荧光显微镜进一步调查的特异性和动力学的金属影响的PrPC贩运和确定的细胞内隔室的内在的PrPC交付响应铜和锌。我们发现，这两种金属刺激重新分配表面PrPC的一个子集的转铁蛋白含有早期内体以及高尔基体。这些结果是一致的模型中，PrPC发挥作用的细胞摄取或流出的过渡金属。
The cellular isoform of prion protein (PrPC) is a plasma membrane glycoprotein whose conformational conversion into PrPSc is the central molecular event in the propagation of infectious prions. However, the physiological function of PrPC has remained uncertain. The finding that PrPC binds copper ions with low micromolar affinity, coupled with several other observations, has led to the proposal that the protein plays a role in copper homeostasis. Using biochemical techniques, we had shown previously that copper ions rapidly and reversibly stimulate endocytosis of PrPC from the cell surface. In this report, we employ immunofluorescence microscopy to further investigate the specificity and kinetics of metal effects on PrPC trafficking and to identify the intracellular compartments to which internalized PrPC is delivered in response to copper and zinc. We find that both of these metals stimulate redistribution of surface PrPC to a subset of transferrin-containing early endosomes as well as to Golgi compartments. These results are consistent with models in which PrPC plays a role in the cellular uptake or efflux of transition metals.