A Drosophila adenosine receptor activates cAMP and calcium signaling
A Drosophila adenosine receptor activates cAMP and calcium signaling
复制标题
DOI：
10.1016/j.ibmb.2006.12.003
复制
发表时间：
2007-04-01
影响因子：
3.8
通讯作者：
Zurovec, Michal
中科院分区：
文献类型：
--
作者：
Dolezelova, Eva;Nothacker, Hans-Peter;Zurovec, Michal
腺苷受体（AdoR）是G蛋白偶联受体超家族的成员，介导胞外腺苷信号转导，但腺苷信号转导的机制尚不清楚。本文报道了一种由果蝇基因CG9753编码的昆虫AdoR的首次鉴定。腺苷刺激携带瞬时表达CG9753的中国仓鼠卵巢细胞导致细胞内cAMP和钙的剂量依赖性增加，但未转染的对照组没有这种反应，表明CG9753编码功能性AdoR。在3龄果蝇幼虫的脑、象盘、环腺和唾液腺中检测到内源性CG9753转录本，体内CG9753过表达可致死性或严重发育异常。这些发育缺陷通过腺苷耗损而减少，这与CG9753产物作为AdoR的功能一致。G蛋白亚基G α (s)或蛋白激酶A （PKA）催化亚基的过表达部分模拟并增强了AdoR异位表达引起的缺陷。我们的研究结果表明，AdoR是腺苷信号通路的重要组成部分，果蝇提供了一个独特的机会，利用遗传分析来研究腺苷信号通路的保守方面。(c) 2007 Elsevier Ltd.版权所有。
Adenosine receptors (AdoR) are members of the G protein-coupled receptor superfamily and mediate extracellular adenosine signaling, but the mechanism of adenosine signaling is still unclear. Here we report the first characterization of an insect AdoR, encoded by the Drosophila gene CG9753. Adenosine stimulation of Chinese hamster ovary cells carrying transiently expressed CG9753 led to a dose-dependent increase of intracellular cAMP and calcium, but untransfected controls showed no such response, showing that CG9753 encodes a functional AdoR. Endogenous CG9753 transcripts were detected in the brain, imaginal discs, ring gland and salivary glands of third-instar Drosophila larvae, and CG9753 overexpression in vivo caused lethality or severe developmental anomalies. These developmental defects were reduced by adenosine depletion, consistent with the proposed function of the CG9753 product as an AdoR. Overexpression of the G protein subunit G alpha(s) or of the catalytic subunit of protein kinase A (PKA) partially mimicked and enhanced the defects caused by ectopic expression of AdoR. Our results suggest that AdoR is an essential part of the adenosine signaling pathway and Drosophila offers a unique opportunity to use genetic analysis to study conserved aspects of the adenosine signaling pathway. (c) 2007 Elsevier Ltd. All rights reserved.