Drosophila short neuropeptide F signalling regulates growth by ERK-mediated insulin signalling
Drosophila short neuropeptide F signalling regulates growth by ERK-mediated insulin signalling
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DOI：
10.1038/ncb1710
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发表时间：
2008-04-01
影响因子：
21.3
通讯作者：
Yu, Kweon
中科院分区：
文献类型：
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作者：
Lee, Kyu-Sun;Kwon, O-Yu;Yu, Kweon
胰岛素和胰岛素生长因子在包括黑腹果蝇在内的动物的生长（1，2）、代谢（3）和衰老（4，5）中具有核心作用。在果蝇中，胰岛素样肽（Dilps）由大脑中的专门神经元产生（3，6）。在这里，我们表明，果蝇短神经肽F（sNPF），哺乳动物神经肽Y（NPY）的直向同源物，和sNPF受体sNPFR 1调节Dilps的表达。sNPF或sNPFR 1的过度表达增加了体型。sNPF突变果蝇脂肪体中Akt表达下调，FOXO定位于细胞核，4 E-BP表达上调，细胞体积缩小。在sNPF突变体中，循环葡萄糖水平升高，寿命也延长。我们发现，这些影响是通过激活幼虫和成虫的胰岛素产生细胞中的细胞外信号相关激酶（ERK）介导的。在培养的果蝇中枢神经系统（CNS）细胞和用sNPF或NPY肽处理的大鼠胰腺细胞中，胰岛素表达也以ERK依赖的方式增加。果蝇sNPF和进化上保守的哺乳动物NPY似乎调节ERK介导的胰岛素表达，从而系统地调节生长、代谢和寿命。
Insulin and insulin growth factor have central roles in growth(1,2), metabolism(3) and ageing(4,5) of animals, including Drosophila melanogaster. In Drosophila, insulin-like peptides ( Dilps) are produced by specialized neurons in the brain(3,6). Here we show that Drosophila short neuropeptide F ( sNPF), an orthologue of mammalian neuropeptide Y ( NPY), and sNPF receptor sNPFR1 regulate expression of Dilps. Body size was increased by overexpression of sNPF or sNPFR1. The fat body of sNPF mutant Drosophila had downregulated Akt, nuclear localized FOXO, upregulated translational inhibitor 4E-BP and reduced cell size. Circulating levels of glucose were elevated and lifespan was also extended in sNPF mutants. We show that these effects are mediated through activation of extracellular signal-related kinases ( ERK) in insulin-producing cells of larvae and adults. Insulin expression was also increased in an ERK-dependent manner in cultured Drosophila central nervous system ( CNS) cells and in rat pancreatic cells treated with sNPF or NPY peptide, respectively. Drosophila sNPF and the evolutionarily conserved mammalian NPY seem to regulate ERK- mediated insulin expression and thus to systemically modulate growth, metabolism and lifespan.