Crosstalk between GABAB and mGlu1a receptors reveals new insight into GPCR signal integration
Crosstalk between GABAB and mGlu1a receptors reveals new insight into GPCR signal integration
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DOI：
10.1038/emboj.2009.177
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发表时间：
2009-08-05
期刊：
影响因子：
11.4
通讯作者：
Prezeau, Laurent
中科院分区：
文献类型：
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作者：
Rives, Marie-Laure;Vol, Claire;Prezeau, Laurent
G蛋白偶联受体（GPCRs）在细胞间通讯中具有重要功能。尽管在相同的细胞中已经鉴定出了各种不同的受体，但信号整合的机制仍然难以捉摸。GPCR形成二聚体或更大的异源寡聚体的能力被认为产生这种信号整合。我们研究了浦肯野神经元中GABA（B）受体介导的mGlu受体信号增强的分子机制。我们表明，这种效应不需要两种受体之间的物理相互作用。相反，这是一种更普遍的机制的结果，其中由Gi偶联GABA（B）受体产生的β γ亚单位增强mGlu介导的Gq反应。最重要的是，这种机制通常可以应用于其他成对的Gi和Gq偶联受体，并且信号整合根据每个受体激活之间的时间延迟而变化。这种机制有助于解释细胞表达由单一递质激活的两种不同的Gi和Gq偶联受体的特定特性，或天然偶联到两种类型G蛋白的GPCR的特性。The EMBO Journal（2009）28，2195-2208. doi：10.1038/doj.2009.177; 2009年7月9日在线发布
G protein-coupled receptors (GPCRs) have critical functions in intercellular communication. Although a wide range of different receptors have been identified in the same cells, the mechanism by which signals are integrated remains elusive. The ability of GPCRs to form dimers or larger hetero-oligomers is thought to generate such signal integration. We examined the molecular mechanisms responsible for the GABA(B) receptor-mediated potentiation of the mGlu receptor signalling reported in Purkinje neurons. We showed that this effect does not require a physical interaction between both receptors. Instead, it is the result of a more general mechanism in which the beta gamma subunits produced by the Gi-coupled GABA(B) receptor enhance the mGlu-mediated Gq response. Most importantly, this mechanism could be generally applied to other pairs of Gi- and Gq-coupled receptors and the signal integration varied depending on the time delay between activation of each receptor. Such a mechanism helps explain specific properties of cells expressing two different Gi-and Gq-coupled receptors activated by a single transmitter, or properties of GPCRs naturally coupled to both types of the G protein. The EMBO Journal (2009) 28, 2195-2208. doi:10.1038/emboj.2009.177; Published online 9 July 2009