Rapid, nongenomic responses to ecdysteroids and catecholamines mediated by a novel Drosophila G-protein-coupled receptor
Rapid, nongenomic responses to ecdysteroids and catecholamines mediated by a novel Drosophila G-protein-coupled receptor
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DOI：
10.1523/jneurosci.1005-05.2005
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发表时间：
2005-06-29
影响因子：
5.3
通讯作者：
Evans, PD
中科院分区：
文献类型：
--
作者：
Srivastava, DP;Yu, EJ;Evans, PD
非基因组反应途径介导了类固醇激素的许多快速作用，但这些反应背后的机制仍然存在争议。在某些情况下，经典的核类固醇受体的细胞表面表达被认为介导了这些效应，但在少数情况下，特定的G蛋白偶联受体(GPCRs)被报道起作用。在这里，我们描述了昆虫蜕皮激素(E)和20-羟基蜕皮酮(20E)对一种新的神经元表达的果蝇GPCRs的激活作用。这是首次发现昆虫GPCR与类固醇相互作用的报道。果蝇的多巴胺/蜕皮激素受体(DmtopEcR)与脊椎动物的β-肾上腺素能受体具有序列同源性，并被多巴胺(DA)激活，以增加cAMP水平并激活磷脂酰肌醇3-激酶途径。相反，E和20E在结合研究中显示出与受体的高亲和力，并可以抑制DA的作用，以及将受体偶联到丝裂原激活的蛋白激酶途径的快速激活。因此，该受体可能代表了脊椎动物“伽马-肾上腺素能受体”的果蝇同系物，该受体负责调节大脑、血管和胰腺的各种活动。因此，在成熟的成人神经系统的发育和信号传递过程中，DmtopEcR可以作为细胞表面的GPCR发挥作用，可能与蜕皮激素的一些快速的、非基因组的作用有关。
Nongenomic response pathways mediate many of the rapid actions of steroid hormones, but the mechanisms underlying such responses remain controversial. In some cases, cell-surface expression of classical nuclear steroid receptors has been suggested to mediate these effects, but, in a few instances, specific G-protein-coupled receptors (GPCRs) have been reported to be responsible. Here, we describe the activation of a novel, neuronally expressed Drosophila GPCR by the insect ecdysteroids ecdysone (E) and 20-hydroxyecdysone (20E). This is the first report of an identified insect GPCR interacting with steroids. The Drosophila melanogaster dopamine/ecdysteroid receptor (DmDopEcR) shows sequence homology with vertebrate beta-adrenergic receptors and is activated by dopamine (DA) to increase cAMP levels and to activate the phosphoinositide 3-kinase pathway. Conversely, E and 20E show high affinity for the receptor in binding studies and can inhibit the effects of DA, as well as coupling the receptor to a rapid activation of the mitogen-activated protein kinase pathway. The receptor may thus represent the Drosophila homolog of the vertebrate "gamma-adrenergic receptors," which are responsible for the modulation of various activities in brain, blood vessels, and pancreas. Thus, DmDopEcR can function as a cell-surface GPCR that may be responsible for some of the rapid, nongenomic actions of ecdysteroids, during both development and signaling in the mature adult nervous system.