Ca2+ activity at GABAB receptors constitutively promotes metabotropic glutamate signaling in the absence of GABA
Ca2+ activity at GABAB receptors constitutively promotes metabotropic glutamate signaling in the absence of GABA
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DOI：
10.1073/pnas.0405387101
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发表时间：
2004-11-30
影响因子：
11.1
通讯作者：
Kano, M
中科院分区：
文献类型：
--
作者：
Tabata, T;Araishi, K;Kano, M
B型γ-氨基丁酸受体（GABA（B）R）是一种G蛋白偶联受体，其调节整个大脑的神经递质释放和神经元兴奋性。在各种神经元中，GABA（B）Rs集中在兴奋性突触。虽然这些受体被认为是响应GABA溢出从相邻的抑制性突触，其功能尚未完全理解。在这里，我们显示了一个以前未描述的功能的GABA（B）R独立发挥GABA。在小脑浦肯野细胞中，GABA（B）R与细胞外Ca 2+（Ca-o（2+））的相互作用导致代谢型谷氨酸受体1（mGluR 1）的谷氨酸敏感性的组成性增加。mGluR 1敏化明显由GABABR介导，因为它在GABA（B）R1亚基敲除细胞中不存在。然而，mGIuR 1致敏不需要G（i/o）蛋白介导GABABR的经典功能。此外，免疫共沉淀揭示了GABA（B）R和nl在小脑中的复合物形成。这些结果表明，GABA（B）R可以作为钙依赖性的辅因子，以增强神经元代谢型谷氨酸信号。
Type B gamma-aminobutyric acid receptor (GABA(B)R) is a G protein-coupled receptor that regulates neurotransmitter release and neuronal excitability throughout the brain. In various neurons, GABA(B)Rs are concentrated at excitatory synapses. Although these receptors are assumed to respond to GABA spillover from neighboring inhibitory synapses, their function is not fully understood. Here we show a previously undescribed function of GABA(B)R exerted independent of GABA. In cerebellar Purkinje cells, interaction of GABA(B)R with extracellular Ca2+ (Ca-o(2+)) leads to a constitutive increase in the glutamate sensitivity of metabotropic glutamate receptor 1 (mGluR1). mGluR1 sensitization is clearly mediated by GABABR because it is absent in GABA(B)R1 subunit-knockout cells. However, the mGIuR1 sensitization does not require G(i/o) proteins that mediate the GABABR's classical functions. Moreover, coimmunoprecipitation reveals complex formation between GABA(B)R and nl in the cerebellum. These findings demonstrate that GABA(B)R can act as Ca-o(2+)-dependent cofactors to enhance neuronal metabotropic glutamate signaling.