罗多普辛家族受体与小G蛋白结合,激活D脂酶
R Mitchell1, D McCulloch, E Lutz
1MRC Brain Metabolism Unit, Edinburgh, UK. rmitchell@srv1.bmu.mrc.ac.uk
Nature
|April 16, 1998
概括
G蛋白结合受体 (GPCRs) 通过小G蛋白ARF和RhoA激活脂酶D. GPCR中的特定氨基酸基因决定了这种相互作用,影响神经和内分泌信号传递.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 生物化学 生物化学
背景情况:
- G蛋白结合受体 (GPCRs) 对于神经和内分泌信号传递至关重要.
- GPCRs激活异构三基G蛋白,也可以调节脂酶D (PLD) 的活性.
- PLD可以通过小G蛋白调节,包括ARF和RhoA.
研究的目的:
- 研究小G蛋白ARF和RhoA在GPCR介导的D脂酶激活中的作用.
- 确定GPCRs内部的结构决定因素,这些因素决定了它们与ARF和RhoA.的相互作用.
- 阐明特定GPCR激活PLD的机制.
主要方法:
- 同免疫沉降测定检测受体-G蛋白相互作用.
- 用GTP模拟结合试验来评估受体-G蛋白合.
- 位点定向的突变发生改变GPCRs内部的特定氨基酸序列.
- 使用ARF和RhoA抑制剂的药理抑制研究.
主要成果:
- 许多Ca2+调动的GPCR以ARF和RhoA依赖的方式激活脂酶D.
- 与ARF/RhoA相互作用的GPCR在其第七个跨膜域中具有AsnProXXTyr动机.
- 独立于ARF激活PLD的GPCR含有AspProXXTyr动机.
- 在GnRHR中将AspProXXTyr转变为AsnProXXTyr赋予了ARF抑制剂的敏感性;在5-HT2A受体中的反向突变降低了敏感性.
结论:
- 在GPCRs中的AsnProXXTyr动机对于与ARF和RhoA形成功能复合物至关重要.
- 这种动机决定了ARF和RhoA在GPCR介导的脂酶D激活中的参与.
- GPCRs的结构变异决定了它们涉及小G蛋白的信号通路.
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