Evidence of presynaptic location and function of the prion protein
Evidence of presynaptic location and function of the prion protein
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DOI：
10.1523/jneurosci.19-20-08866.1999
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发表时间：
1999-10-15
影响因子：
5.3
通讯作者：
Kretzschmar, H
中科院分区：
文献类型：
--
作者：
Herms, J;Tings, T;Kretzschmar, H
PrPC是一种功能未知的铜结合蛋白，在传染性海绵状脑病的病因学中起重要作用。利用形态技术和突触小体分离方法，我们发现PrPC主要定位于突触膜上。原子吸收光谱被用来鉴定转基因小鼠品系中突触体铜浓度的PrPC相关变化。在这些动物中，研究了H_2O_2存在下的突触传递，已知在铁或铜存在下，H_2O_2会分解成高活性的羟基自由基，并改变突触活性。在野生型、PRNP(0/0)和PrP基因重组转基因小鼠的小脑切片中，突触活性对H_2O_2的反应与突触前神经元中PrPC的表达量相关。因此，我们的数据为PrPC的主要突触位置提供了强有力的证据，它参与了突触前铜浓度的调节，以及在特定条件下的突触活动。
The prion protein (PrPC) is a copper-binding protein of unknown function that plays an important role in the etiology of transmissible spongiform encephalopathies. Using morphological techniques and synaptosomal fractionation methods, we show that PrPC is predominantly localized to synaptic membranes. Atomic absorption spectroscopy was used to identify PrPC-related changes in the synaptosomal copper concentration in transgenic mouse lines. The synaptic transmission in the presence of H2O2, which is known to be decomposed to highly reactive hydroxyl radicals in the presence of iron or copper and to alter synaptic activity, was studied in these animals. The response of synaptic activity to H2O2 was found to correlate with the amount of PrPC expression in the presynaptic neuron in cerebellar slice preparations from wild-type, Prnp(0/0), and PrP gene-reconstituted transgenic mice. Thus, our data gives strong evidence for the predominantly synaptic location of PrPC, its involvement in the regulation of the presynaptic copper concentration, and synaptic activity in defined conditions.