We have previously reported that cellular prion protein (PrPC) can down-regulate NMDA receptor activity and in a copper dependent manner. Here, we employed AAV9 to introduce murine cellular prion protein into mouse hippocampal neurons in primary cultures from PrP null mice to determine the role of the six copper binding motifs located within the N-terminal domain of PrPC. The results demonstrate that viral expression of wild type PrPC lowers NMDAR activity in PrP null mouse hippocampal neurons by reducing the magnitude of non-desensitizing currents. Elimination of the last two copper binding sites alone, or in combination with the remaining four attenuates this protective effect. Thus our data suggest that copper ion interactions with specific binding sites on PrPC are critical for PrPC dependent modulation of NMDA receptor function.

中文翻译：

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细胞朊病毒蛋白上铜结合位点的突变消除了其对小鼠海马神经元 NMDA 受体的抑制作用


我们之前报道过细胞朊病毒蛋白（PrPC）可以以铜依赖性方式下调 NMDA 受体活性。在这里，我们利用 AAV9 将鼠细胞朊病毒蛋白引入 PrP 缺失小鼠原代培养物中的小鼠海马神经元中，以确定位于 PrPC N 端结构域内的六个铜结合基序的作用。结果表明，野生型 PrPC 的病毒表达通过降低非脱敏电流的幅度来降低 PrP 无效小鼠海马神经元中的 NMDAR 活性。单独消除最后两个铜结合位点或与其余四个结合位点一起消除会减弱这种保护作用。因此，我们的数据表明，铜离子与 PrPC 上特定结合位点的相互作用对于 NMDA 受体功能的 PrPC 依赖性调节至关重要。