moody Encodes two GPCRs that regulate cocaine behaviors and blood-brain barrier permeability in Drosophila
moody Encodes two GPCRs that regulate cocaine behaviors and blood-brain barrier permeability in Drosophila
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DOI：
10.1016/j.cell.2005.07.029
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发表时间：
2005-10-07
期刊：
影响因子：
64.5
通讯作者：
Heberlein, U
中科院分区：
文献类型：
--
作者：
Bainton, RJ;Tsai, LTY;Heberlein, U
我们在对可卡因敏感性改变的果蝇突变体的基因筛选中发现了穆迪。穆迪的次胚突变会增加对可卡因和尼古丁的敏感性。相反，对乙醇急性中毒作用的敏感性降低。moody基因座编码两种新的gpcr， moody - α和moody - β。虽然这两种Moody蛋白的跨膜结构域是相同的，但它们的长羧基末端结构域是不同的，这是通过使用不同的阅读框架产生的。这两种穆迪型都是正常可卡因敏感性所必需的，这表明它们具有不同但互补的功能。moody - α和moody - β在神经系统周围的表面胶质细胞中共同表达，在成年果蝇中，它们被积极地要求维持血脑屏障的完整性。我们认为moody介导的信号通路在神经胶质细胞中起调节神经系统绝缘和药物相关行为的作用。
We identified moody in a genetic screen for Drosophila mutants with altered cocaine sensitivity. Hypomorphic mutations in moody cause an increased sensitivity to cocaine and nicotine exposure. In contrast, sensitivity to the acute intoxicating effects of ethanol is reduced. The moody locus encodes two novel GPCRs, Moody-alpha and Moody-beta. While identical in their membrane-spanning domains, the two Moody proteins differ in their long carboxy-terminal domains, which are generated by use of alternative reading frames. Both Moody forms are required for normal cocaine sensitivity, suggesting that they carry out distinct but complementary functions. Moody-alpha and Moody-beta are coexpressed in surface glia that surround the nervous system, where they are actively required to maintain the integrity of the blood-brain barrier in the adult fly. We propose that a Moody-mediated signaling pathway functions in glia to regulate nervous system insulation and drug-related behaviors.