In neuronal cells, many membrane receptors interact via their intracellular, C-terminal tails with PSD-95/discs large/ZO-1 (PDZ) domain proteins. Some PDZ proteins act as scaffold proteins. In addition, there are a few PDZ proteins such as Gopc which bind to receptors during intracellular transport. Gopc is localized at the trans-Golgi network (TGN) and binds to a variety of receptors, many of which are eventually targeted to postsynaptic sites. We have analyzed the role of Gopc by knockdown in primary cultured neurons and by generating a conditional Gopc knockout (KO) mouse line. In neurons, targeting of neuroligin 1 (Nlgn1) and metabotropic glutamate receptor 5 (mGlu5) to the plasma membrane was impaired upon depletion of Gopc, whereas NMDA receptors were not affected. In the hippocampus and cortex of Gopc KO animals, expression levels of Gopc-associated receptors were not altered, while their subcellular localization was disturbed. The targeting of mGlu5 to the postsynaptic density was reduced, coinciding with alterations in mGluR-dependent synaptic plasticity and deficiencies in a contextual fear conditioning paradigm. Our data imply Gopc in the correct subcellular sorting of its associated mGlu5 receptor in vivo.

在神经元细胞中，许多膜受体通过其细胞内的 C 末端尾部与 PSD-95/大圆盘相互作用/ZO-1 (PDZ) 结构域蛋白。一些 PDZ 蛋白充当支架蛋白。此外，还有一些 PDZ 蛋白（如 Gopc）在细胞内转运过程中与受体结合。Gopc 定位于跨高尔基网络 (TGN) 并与多种受体结合，其中许多受体最终靶向突触后位点。我们通过在原代培养的神经元中敲低和生成条件性 Gopc 敲除 (KO) 小鼠系来分析 Gopc 的作用。在神经元中，Gopc 耗竭后，neuroligin 1 (Nlgn1) 和代谢型谷氨酸受体 5 (mGlu5) 对质膜的靶向作用受损，而 NMDA 受体不受影响。在 Gopc KO 动物的海马和皮质中，Gopc 相关受体的表达水平没有改变，而它们的亚细胞定位受到干扰。mGlu5 对突触后密度的靶向性降低，与 mGluR 依赖性突触可塑性的变化和上下文恐惧条件范式的缺陷相吻合。我们的数据暗示 Gopc 在体内对其相关的 mGlu5 受体进行正确的亚细胞分类。