Copper stimulates endocytosis of the prion protein
Copper stimulates endocytosis of the prion protein
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DOI：
10.1074/jbc.273.50.33107
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发表时间：
1998-12-11
影响因子：
4.8
通讯作者：
Harris, DA
中科院分区：
文献类型：
--
作者：
Pauly, PC;Harris, DA
PrPC是一种细胞表面糖蛋白，在脑、脊髓和一些外周组织中表达，PrPSc是一种蛋白酶抗性异构体，是感染性朊病毒颗粒的主要成分，PrPC的构象改变导致了朊病毒疾病。虽然人们对PrPSc的致病作用已经了解很多，但PrPC的生理功能仍然是一个谜。最近有几条证据表明，PrPC可能在铜的代谢中发挥作用。为了进一步研究PrPC和铜的相互作用，我们分析了这种金属离子对PrPC在培养的神经母细胞瘤细胞内吞运输的影响，我们在这里报道了铜从细胞表面快速可逆地刺激PrPC的内吞作用。这种效应可能与生理相关，并提出了PrPC可以作为从细胞外环境中吸收铜离子的再循环受体的假设。
Prion diseases result from conformational alteration of PrPC, a cell surface glycoprotein expressed in brain, spinal cord, and several peripheral tissues, into PrPSc, a protease-resistant isoform that is the principal component of infectious prion particles. Although a great deal is known about the pathogenic role of PrPSc, the physiological function of PrPC has remained a mystery. Several lines of evidence have recently suggested the possibility that PrPC may play a role in the metabolism of copper. To further investigate the interaction of PrPC and copper, we have analyzed the effect of this metal ion on the endocytic trafficking of PrPC in cultured neuroblastoma cells, We report here that copper rapidly and reversibly stimulates endocytosis of PrPC from the cell surface. This effect may be physiologically relevant and suggests the hypothesis that PrPC could serve as a recycling receptor for uptake of copper ions from the extracellular milieu.