Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs.
Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs.
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DOI：
10.1371/journal.pone.0003721
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Partridge L
中科院分区：
文献类型：
--
作者：
Broughton S;Alic N;Slack C;Bass T;Ikeya T;Vinti G;Tommasi AM;Driege Y;Hafen E;Partridge L
胰岛素/ igf样信号通路（IIS）在所有多细胞生物中具有多种功能，包括决定寿命。7种胰岛素样肽（dilp）在果蝇中以阶段和组织特异性的方式表达。大脑中产生三种dilp的正中神经分泌细胞（mNSCs）部分消融可延长寿命，降低生殖力，改变脂质和碳水化合物代谢，增强氧化应激抵抗能力。为了确定dilp的表达减少是否导致了这些影响，并研究dilp之间可能的功能多样化和冗余，我们使用RNA干扰来特异性降低dilp2的转录物和蛋白水平，dilp2是mnscs衍生的dilp中表达最高的。我们发现DILP2仅限制与mscs消融相关的全身海藻糖含量增加。我们观察到dilp3和5mrna在dilp2敲除后代偿性增加。通过操纵dfoxo和dInR，我们发现dilp3的增加是通过mscs中的自分泌胰岛素信号来调节的。我们的研究表明，尽管dilp2 mRNA水平的降低与寿命延长之间存在相关性，但dilp2的降低并不足以延长寿命。与降低IIS相关的海藻糖存储的增加也不足以延长生命周期。要了解dilps的正常表达调控以及它们之间的功能分化，需要对不同dilps的表达进行独立控制。
The insulin/IGF-like signalling (IIS) pathway has diverse functions in all multicellular organisms, including determination of lifespan. The seven insulin-like peptides (DILPs) in Drosophila are expressed in a stage- and tissue-specific manner. Partial ablation of the median neurosecretory cells (mNSCs) in the brain, which produce three DILPs, extends lifespan, reduces fecundity, alters lipid and carbohydrate metabolism and increases oxidative stress resistance. To determine if reduced expression of DILPs is causal in these effects, and to investigate possible functional diversification and redundancy between DILPs, we used RNA interference to lower specifically the transcript and protein levels of dilp2, the most highly expressed of the mNSC-derived DILPs. We found that DILP2 was limiting only for the increased whole-body trehalose content associated with mNSC-ablation. We observed a compensatory increase in dilp3 and 5 mRNA upon dilp2 knock down. By manipulation of dfoxo and dInR, we showed that the increase in dilp3 is regulated via autocrine insulin signaling in the mNSCs. Our study demonstrates that, despite the correlation between reduced dilp2 mRNA levels and lifespan-extension often observed, DILP2 reduction is not sufficient to extend lifespan. Nor is the increased trehalose storage associated with reduced IIS sufficient to extend lifespan. To understand the normal regulation of expression of the dilps and any functional diversification between them will require independent control of the expression of different dilps.
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影响因子：
9.2
作者：
Brogiolo, W;Stocker, H;Hafen, E
通讯作者：
Hafen, E
影响因子：
3.5
作者：
Mattaliano, Mark D.;Montana, Enrico S.;Griffith, Leslie C.
通讯作者：
Griffith, Leslie C.
影响因子：
56.9
作者：
Mair, W;Goymer, P;Partridge, L
通讯作者：
Partridge, L
DOI：
10.1002/neu.20193
发表时间：
2006-01-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Belgacem, YH;Martin, JR
通讯作者：
Martin, JR
DOI：
10.1073/pnas.0405775102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Broughton, SJ;Piper, MDW;Partridge, L
通讯作者：
Partridge, L