Couve A, Filippov A K, Connolly C N, Bettler B, Brown D A, Moss S J
Medical Research Council Laboratory of Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
J Biol Chem. 1998 Oct 9;273(41):26361-7. doi: 10.1074/jbc.273.41.26361.
gamma-Aminobutyric acid type B (GABAB) receptors mediate the transmission of slow and prolonged inhibitory signals in the central nervous system. Two splice variants of GABAB receptors, GABABR1a and GABABR1b, were recently cloned from a mouse cortical and cerebellar cDNA library. As predicted, these receptors belong to the G protein-coupled receptor superfamily. We have used epitope-tagged versions of GABABR1a receptors to study the cellular distribution of these proteins in a variety of non-neuronal and neuronal cell types. Here we report that recombinant GABAB receptors fail to reach the cell surface when expressed in heterologous systems and are retained in the endoplasmic reticulum when introduced into COS cells. In addition, we prove that recombinant GABAB receptors are excluded from the cell surface when overexpressed in ganglion neurons and we further demonstrate that they fail to activate in superior cervical ganglion neurons. Together our observations suggest that recombinant GABAB receptors require additional information for functional targeting to the plasma membrane.
γ-氨基丁酸B型（GABAB）受体介导中枢神经系统中缓慢而持久的抑制性信号传递。最近从小鼠皮质和小脑cDNA文库中克隆出了GABAB受体的两种剪接变体，即GABABR1a和GABABR1b。正如所预测的，这些受体属于G蛋白偶联受体超家族。我们使用了带有表位标签的GABABR1a受体版本，来研究这些蛋白质在多种非神经元和神经元细胞类型中的细胞分布。在此我们报告，重组GABAB受体在异源系统中表达时无法到达细胞表面，当导入COS细胞时会保留在内质网中。此外，我们证明重组GABAB受体在神经节神经元中过表达时会被排除在细胞表面，并且我们进一步证明它们在上颈神经节神经元中无法激活。我们的观察结果共同表明，重组GABAB受体需要额外的信息才能功能性地靶向质膜。
