Identification of a Novel Gene, Anorexia, Regulating Feeding Activity via Insulin Signaling in Drosophila melanogaster
Identification of a Novel Gene, Anorexia, Regulating Feeding Activity via Insulin Signaling in Drosophila melanogaster
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DOI：
10.1074/jbc.m111.267344
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发表时间：
2011-11-04
影响因子：
4.8
通讯作者：
Hayakawa, Yoichi
中科院分区：
文献类型：
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作者：
Ryuda, Masasuke;Tsuzuki, Seiji;Hayakawa, Yoichi
包括昆虫在内的动物的摄食活动受到来自外部环境、内部能量状态和生理条件的各种信号的影响。然而，由于缺乏对相关基因的了解，对这些信号如何整合以调节摄食活动的充分理解受到了阻碍。在这里，我们确定了一个新发现的基因，厌食症（Anox）的表达突变的黑腹果蝇突变体（GS 1189）。在果蝇幼虫中，Anox编码具有锚蛋白重复结构域的酰基辅酶A结合蛋白，其在头部化学感受器和中枢神经系统（CNS）中的各种神经元中表达。其表达的损失或Anox表达细胞中的神经传递的干扰降低了摄食活性。相反，CNS中Anox的过度表达增加了食物摄入。我们进一步发现，Anox调节胰岛素受体基因（dInR）的表达;在中枢神经系统中，过表达和敲低Anox，分别升高和抑制dInR的表达，这改变了幼虫的摄食活动与Anox表达水平平行。Anox突变体成虫也表现出显着的抑制糖诱导的神经反应和摄食能力。虽然Anox的表达水平并不依赖于禁食和进食状态的周期，应激，如高温和干燥显着抑制其表达水平。这些结果有力地表明，Anox通过调节由内部营养状态直接调节的胰岛素信号传导活性对果蝇的味觉感觉和食物摄取是必不可少的。因此，缺乏Anox表达的突变株即使在饥饿下也不能增强摄食效力。
Feeding activities of animals, including insects, are influenced by various signals from the external environment, internal energy status, and physiological conditions. Full understanding of how such signals are integrated to regulate feeding activities has, however, been hampered by a lack of knowledge about the genes involved. Here, we identified an anorexic Drosophila melanogaster mutant (GS1189) in which the expression of a newly identified gene, Anorexia (Anox), is mutated. In Drosophila larvae, Anox encodes an acyl-CoA binding protein with an ankyrin repeat domain that is expressed in the cephalic chemosensory organs and various neurons in the central nervous system (CNS). Loss of its expression or disturbance of neural transmission in Anox-expressing cells decreased feeding activity. Conversely, overexpression of Anox in the CNS increased food intake. We further found that Anox regulates expression of the insulin receptor gene (dInR); overexpression and knockdown of Anox in the CNS, respectively, elevated and repressed dInR expression, which altered larval feeding activity in parallel with Anox expression levels. Anox mutant adults also showed significant repression of sugar-induced nerve responses and feeding potencies. Although Anox expression levels did not depend on the fasting and feeding states cycle, stressors such as high temperature and desiccation significantly repressed its expression levels. These results strongly suggest that Anox is essential for gustatory sensation and food intake of Drosophila through regulation of the insulin signaling activity that is directly regulated by internal nutrition status. Therefore, the mutant strain lacking Anox expression cannot enhance feeding potencies even under starvation.