An ER retention signal explains differences in surface expression of NMDA and AMPA receptor subunits
An ER retention signal explains differences in surface expression of NMDA and AMPA receptor subunits
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DOI：
10.1016/s0028-3908(01)00103-4
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发表时间：
2001-11
影响因子：
4.7
通讯作者：
H. Xia;Z. Hornby;R. Malenka
中科院分区：
文献类型：
--
作者：
H. Xia;Z. Hornby;R. Malenka
控制NMDA受体（NMDAR）和AMPA受体（AMPAR）表面表达的分子机制尚不清楚。为了确定谷氨酸受体亚基的细胞内C末端尾部在AMPAR和NMDAR的突触靶向中的作用，我们将AMPAR亚基GluR 1和GluR 2以及NMDAR亚基NR 1的尾部融合到人T淋巴细胞膜蛋白CD 8上，并在HEK 293细胞和培养的海马神经元中表达这些构建体。GluR 1和GluR 2融合蛋白在突触处的神经元质膜中表现出稳健的表面表达，如单独的CD 8。相反，NR 1融合蛋白保留在HEK 293细胞和神经元细胞内，因为C1盒中存在ER保留信号。该ER滞留信号通过添加PDZ结构域结合基序或通过模拟滞留信号附近位点的磷酸化而被覆盖。这些结果提供了进一步的证据，AMPAR和NMDAR亚基的细胞内运输独立地调节，至少部分是因为它们的细胞内C-末端尾部的蛋白质-蛋白质相互作用的差异。
The molecular mechanisms that control the surface expression of NMDA receptors (NMDARs) and AMPA receptors (AMPARs) are unknown. To determine the role of the intracellular C-terminal tails of glutamate receptor subunits in the synaptic targeting of AMPARs and NMDARs, we fused the tails of the AMPAR subunits, GluR1 and GluR2, and the NMDAR subunit, NR1, to the human T lymphocyte membrane protein CD8 and expressed these constructs in HEK293 cells and cultured hippocampal neurons. The GluR1 and GluR2 fusion proteins exhibited robust surface expression in the plasma membrane of neurons at synapses as did CD8 alone. In contrast, the NR1 fusion protein was retained intracellularly in both HEK293 cells and neurons because of the presence of an ER retention signal in the C1 cassette. This ER retention signal was overridden either by the addition of a PDZ domain-binding motif or by mimicking phosphorylation at a site adjacent to the retention signal. These results provide further evidence that the intracellular trafficking of AMPAR and NMDAR subunits are regulated independently at least in part because of differences in the protein–protein interactions of their intracellular C-terminal tails.