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首页> 美国卫生研究院文献>The EMBO Journal >Role of the PLC-related catalytically inactive protein p130 in GABAA receptor function
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Role of the PLC-related catalytically inactive protein p130 in GABAA receptor function

机译：PLC相关的催化失活蛋白p130在GABAA受体功能中的作用

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摘要

The protein p130 was isolated from rat brain as an inositol 1,4,5-trisphosphate-binding protein with a domain organization similar to that of phospholipase C-δ1 but lacking PLC activity. We show that p130 plays an important role in signaling by the type A receptor for γ-aminobutyric acid (GABA). Yeast twohybrid screening identified GABARAP (GABAA receptor-associated protein), which is proposed to contribute to the sorting, targeting or clustering of GABAA receptors, as a protein that interacts with p130. Furthermore, p130 competitively inhibited the binding of the γ2 subunit of the GABAA receptor to GABARAP in vitro. Electrophysiological analysis revealed that the modulation of GABA-induced Cl– current by Zn2+ or diazepam, both of which act at GABAA receptors containing γ subunits, is impaired in hippocampal neurons of p130 knockout mice. Moreover, behavioral analysis revealed that motor coordination was impaired and the intraperitoneal injection of diazepam induced markedly reduced sedative and antianxiety effects in the mutant mice. These results indicate that p130 is essential for the function of GABAA receptors, especially in response to the agents acting on a γ2 subunit.
机译：从大鼠脑中分离出的蛋白p130是肌醇1,4,5-三磷酸结合蛋白，其结构域类似于磷脂酶C-δ1，但缺乏PLC活性。我们证明p130在γ-氨基丁酸（GABA）的A型受体信号传导中起着重要作用。酵母双杂交筛选确定了GABARAP（GABAA受体相关蛋白），被认为有助于GABAA受体的分选，靶向或聚类，是一种与p130相互作用的蛋白。此外，p130在体外竞争性抑制GABAA受体的γ2亚基与GABARAP的结合。电生理分析表明，海马神经元中的Zn 2 + 或地西m对GABA诱导的Cl – 电流的调节均受损，这两种电流均作用于含有γ亚基的GABAA受体。 p130基因敲除小鼠。此外，行为分析表明，运动协调性受到损害，腹膜内注射地西induced可明显降低突变小鼠的镇静和抗焦虑作用。这些结果表明，p130对于GABAA受体的功能是必不可少的，特别是在对作用于γ2亚基的药剂的响应中。

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