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Ric-8A a Gα Protein Guanine Nucleotide Exchange Factor Potentiates Taste Receptor Signaling

机译:Ric-8A一种Gα蛋白鸟嘌呤核苷酸交换因子可增强味觉信号。

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摘要

Taste receptors for sweet, bitter and umami tastants are G-protein-coupled receptors (GPCRs). While much effort has been devoted to understanding G-protein-receptor interactions and identifying the components of the signalling cascade downstream of these receptors, at the level of the G-protein the modulation of receptor signal transduction remains relatively unexplored. In this regard a taste-specific regulator of G-protein signaling (RGS), RGS21, has recently been identified. To study whether guanine nucleotide exchange factors (GEFs) are involved in the transduction of the signal downstream of the taste GPCRs we investigated the expression of Ric-8A and Ric-8B in mouse taste cells and their interaction with G-protein subunits found in taste buds. Mammalian Ric-8 proteins were initially identified as potent GEFs for a range of Gα subunits and Ric-8B has recently been shown to amplify olfactory signal transduction. We find that both Ric-8A and Ric-8B are expressed in a large portion of taste bud cells and that most of these cells contain IP3R-3 a marker for sweet, umami and bitter taste receptor cells. Ric-8A interacts with Gα-gustducin and Gαi2 through which it amplifies the signal transduction of hTas2R16, a receptor for bitter compounds. Overall, these findings are consistent with a role for Ric-8 in mammalian taste signal transduction.
机译:甜味,苦味和鲜味的味觉受体是G蛋白偶联受体(GPCR)。尽管已经付出了很多努力来理解G蛋白受体相互作用,并确定这些受体下游的信号级联反应的组成部分,但在G蛋白水平上,受体信号转导的调节仍然相对未开发。在这方面,最近已经确定了G蛋白信号传导(RGS)的味觉特异性调节剂RGS21。为了研究鸟嘌呤核苷酸交换因子(GEF)是否参与味觉GPCR下游信号的转导,我们研究了Ric-8A和Ric-8B在小鼠味觉细胞中的表达以及它们与味觉中发现的G蛋白亚基的相互作用芽。最初,哺乳动物Ric-8蛋白被鉴定为针对一系列Gα亚基的有效GEF,最近已显示Ric-8B可放大嗅觉信号转导。我们发现Ric-8A和Ric-8B都在大部分味蕾细胞中表达,并且大多数这些细胞都含有IP3R-3,这是甜味,鲜味和苦味受体细胞的标记。 Ric-8A与Gα-gustducin和Gαi2相互作用,通过它可以放大hTas2R16(一种苦味化合物的受体)的信号转导。总体而言,这些发现与Ric-8在哺乳动物味觉信号转导中的作用一致。

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