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首页> 外文期刊>Cellular Signalling >Selective interactions between G protein subunits and RGS4 with the C-terminal domains of the mu- and delta-opioid receptors regulate opioid receptor signaling
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Selective interactions between G protein subunits and RGS4 with the C-terminal domains of the mu- and delta-opioid receptors regulate opioid receptor signaling

机译：G蛋白亚基和RGS4与mu和delta阿片受体的C末端结构域之间的选择性相互作用调节阿片受体的信号传导

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To define receptor subdomains important for protein interaction and identify components of novel signal transduction complexes for the mu- and delta-opioid receptors (mu-OR, delta-OR), we generated glutathione S-transferase fusion proteins of the carboxyl-termini of the mu-opioid receptor (mu-CT), the delta- (delta-CT), and the third intracellular loop of the delta-opioid receptor (delta-i3L) to search for interactive proteins. Results from pull down experiments have demonstrated for the first time that G beta gamma complexes, derived from the heterotrimeric G alpha t beta l gamma l, purified G beta l gamma l, or G beta endogenously present in cell lysates and rat striatal extracts, interact with all mu- and delta-opioid receptor subdomains. On the other hand, the C-terminal peptides of the delta- and the mu-ORs exhibit differential profiles for G alpha subunit binding. Indeed, while mu-CT was unable to bind any form of G alpha, both the delta-CT and the delta-i3L displayed interactive regions for heterotrimeric G alpha t beta l gamma l, inactive G alpha(GDP) and active G alpha(GTP gamma S). Regulators of G protein signaling (RGS) proteins are another class of proteins that can modulate G protein signaling events. We demonstrate for the first time that RGS4 directly interacts with the mu-CT, the delta-CT as well as delta-i3L in a dose dependent manner. Moreover, RGS4 modulates mu-OR signaling and can form stable heterotrimeric complexes with the activated G alpha. Collectively, our data demonstrate that the C-termini of the mu- and delta-ORs provide direct physical scaffolding in which G protein subunits and RGS4 protein can be bound. (c) 2005 Elsevier Inc. All rights reserved.
机译：为了定义对蛋白质相互作用重要的受体亚结构域，并确定新的信号转导复合物的mu和del阿片类受体（mu-OR，delta-OR）的成分，我们生成了谷胱甘肽S-转移酶的谷胱甘肽S-转移酶融合蛋白。 mu阿片受体（mu-CT），delta-（delta-CT）和delta-阿片类受体的第三个细胞内环（delta-i3L）来寻找相互作用的蛋白质。下拉实验的结果首次证明，源自细胞裂解物和大鼠纹状体提取物中的异源三聚体G alpha t beta1 gammal，纯化的G beta 1 gammal或Gβ的Gβγ复合物相互作用具有所有的μ-和δ-阿片受体亚域。另一方面，δ-和mu-OR的C-末端肽表现出Gα亚基结合的差异特征。实际上，虽然mu-CT无法结合任何形式的G alpha，但delta-CT和delta-i3L都显示了异源三聚G alpha t beta 1 gammal，非活性G alpha（GDP）和活性G alpha（ GTP伽玛S）。 G蛋白信号转导（RGS）蛋白的调节剂是另一类可以调节G蛋白信号转导事件的蛋白。我们首次证明RGS4以剂量依赖性方式直接与mu-CT，delta-CT以及delta-i3L相互作用。此外，RGS4调节mu-OR信号传导，并可以与活化的G alpha形成稳定的异三聚体复合物。总体而言，我们的数据表明，mu-和del-OR的C末端提供了直接的物理支架，其中G蛋白亚基和RGS4蛋白可以结合在一起。 （c）2005 Elsevier Inc.保留所有权利。

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