A Drosophila orphan G protein-coupled receptor BOSS functions as a glucose-responding receptor: Loss of boss causes abnormal energy metabolism
A Drosophila orphan G protein-coupled receptor BOSS functions as a glucose-responding receptor: Loss of boss causes abnormal energy metabolism
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DOI：
10.1073/pnas.0807833105
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发表时间：
2008-10-07
影响因子：
11.1
通讯作者：
Hirabayashi, Yoshio
中科院分区：
文献类型：
--
作者：
Kohyama-Koganeya, Ayako;Kim, Yeon-Jeong;Hirabayashi, Yoshio
葡萄糖是动物最重要的营养素之一，充当调节信号，控制内分泌组织分泌胰岛素等激素。然而，生物体如何响应细胞外葡萄糖以及葡萄糖如何控制营养稳态仍然未知。在这里，我们展示了一种假定的黑腹果蝇 G 蛋白偶联受体（之前被鉴定为七人之新娘（BOSS）），对细胞外葡萄糖做出反应并调节糖和脂质代谢。我们发现BOSS在脂肪体（相当于哺乳动物肝脏和脂肪组织的营养感知组织）和感光细胞中表达。 Boss无效突变体体形较小，表现出异常的糖和脂质代谢（循环糖和脂质水平升高，卵细胞的脂质动员受损），并且对营养缺乏应激敏感。这些表型让人想起胰岛素信号传导缺陷的果蝇。与这些发现一致的是，boss 突变体降低了 PI3K 活性和磷酸化 AKT 水平，这表明 BOSS 是正确的胰岛素信号传导所必需的。由于人类 G 蛋白偶联受体 5B 和 BOSS 的七次跨膜结构域具有相同的序列，因此我们的结果对人类葡萄糖代谢也具有重要意义。因此，我们的研究不仅深入了解代谢调节的基本机制，而且还深入了解糖尿病和肥胖的病理生物学基础。
Glucose, one of the most important nutrients for animals, acts as a regulatory signal that controls the secretion of hormones, such as insulin, by endocrine tissues. However, how organisms respond to extracellular glucose and how glucose controls nutrient homeostasis remain unknown. Here, we show that a putative Drosophila melanogaster G protein-coupled receptor, previously identified as Bride of sevenless (BOSS), responds to extracellular glucose and regulates sugar and lipid metabolism. We found that BOSS was expressed in the fat body, a nutrient-sensing tissue equivalent to mammalian liver and adipose tissues, and in photoreceptor cells. Boss null mutants had small bodies, exhibited abnormal sugar and lipid metabolism (elevated circulating sugar and lipid levels, impaired lipid mobilization to oenocytes), and were sensitive to nutrient deprivation stress. These phenotypes are reminiscent of flies defective in insulin signaling. Consistent with these findings are the observations that boss mutants had reduced PI3K activity and phospho-AKT levels, which indicates that BOSS is required for proper insulin signaling. Because human G protein-coupled receptor 5B and the seven-transmembrane domain of BOSS share the same sequence, our results also have important implications for glucose metabolism in humans. Thus, our study provides insight not only into the basic mechanisms of metabolic regulation but also into the pathobiological basis for diabetes and obesity.