Interactions between GABA-B1 receptors and Kir 3 inwardly rectifying potassium channels
Interactions between GABA-B1 receptors and Kir 3 inwardly rectifying potassium channels
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DOI：
10.1016/j.cellsig.2006.05.014
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发表时间：
2006-12-01
影响因子：
4.8
通讯作者：
Hebert, Terence E.
中科院分区：
文献类型：
--
作者：
David, Martin;Richer, Maxime;Hebert, Terence E.
γ-氨基丁酸（GABA）是哺乳动物脑中的主要抑制性神经递质。它通过离子型GABA-A和代谢型GABA-B受体发挥作用。我们评估了受体与内向整流钾（Kir 3）通道家族成员的相互作用，该家族在神经元传递和膜兴奋性中也起着重要作用。这些通道在功能上受GABA-B受体调节。利用生物发光共振能量转移（BRET）实验、免疫共沉淀和共聚焦显微镜技术研究了GABA-B受体与HEK细胞中表达的Kir 3通道之间可能的物理相互作用。我们的数据表明，Kir 3通道和G β γ亚基可以独立于GABA-B-2亚基或Kir 3.4与GABA-B-1亚基相互作用，而GABA-B-2亚基或Kir 3.4最终负责它们靶向细胞表面。因此，含有GABA-B受体、G蛋白和Kir通道的信号传导复合物在生物合成后不久最可能在内质网中形成。(c)2006年爱思唯尔公司All rights reserved.
gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the mammalian brain. It acts via both ionotropic GABA-A and metabotropic GABA-B receptors. We evaluated the interaction of receptors with members of the inwardly rectifying potassium (Kir 3) channel family, which also play an important role in neuronal transmission and membrane excitability. These channels are functionally regulated by GABA-B receptors. Possible physical interactions between GABA-B receptor and Kir 3 channels expressed in HEK cells were evaluated using Bioluminescence Resonance Energy Transfer (BRET) experiments, co-immunoprecipitation and confocal microscopy. Our data indicate that Kir 3 channels and G beta gamma subunits can interact with the GABA-B-1 subunits independently of the GABA-B-2 subunit or Kir 3.4 which are ultimately responsible for their targetting to the cell surface. Thus signalling complexes containing GABA-B receptors, G proteins and Kir channels are formed shortly after biosynthesis most likely in the endoplasmic reticulum. (c) 2006 Elsevier Inc. All rights reserved.