Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance.
Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance.
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DOI：
10.3390/genes12010119
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发表时间：
2021-01-19
期刊：
影响因子：
3.5
通讯作者：
Riehle MA
中科院分区：
文献类型：
--
作者：
Oringanje C;Delacruz LR;Han Y;Luckhart S;Riehle MA
中肠线粒体完整性和内环境平衡是控制蚊子适应性和抗病原体抗性的关键因素。靶向调节线粒体动力学的基因代表了限制蚊媒疾病的潜在策略。amp活化蛋白激酶（AMPK）是几乎在所有真核细胞中发现的关键细胞能量传感器。激活后，AMPK抑制消耗ATP的合成代谢途径，并激活合成ATP的分解代谢过程。在本研究中，我们在雌性斯氏按蚊中肠中特异性羧肽酶启动子的控制下，过表达了AMPK的一个截断的组成活性α-亚基。正如预期的那样，AMPK在纯合子转基因蚊子中的过表达与营养储存和代谢的变化有关，在转基因表达达到最大值的血喂养后24 h糖原水平降低，同时在同一时间点循环海藻糖增加。当转基因系被恶性疟原虫攻击时，我们观察到与野生型对照相比，转基因系的感染率和感染强度显著降低。令人惊讶的是，我们没有观察到仅喂食糖或同时喂食糖和血的成蚊在整个成年期的存活率有显著差异。这可能是由于在稳态恢复之前转基因被激活的时间有限。然而，我们确实观察到产卵量显著减少，这表明对蚊子中肠AMPK活性的操纵导致了产卵资源的重新分配。综上所述，本研究确定了中肠AMPK活性是an的代谢、繁殖和先天免疫的重要调节因子。斯蒂芬氏菌是一种具有高度侵入性的重要疟疾病媒。
Mitochondrial integrity and homeostasis in the midgut are key factors controlling mosquito fitness and anti-pathogen resistance. Targeting genes that regulate mitochondrial dynamics represents a potential strategy for limiting mosquito-borne diseases. AMP-activated protein kinase (AMPK) is a key cellular energy sensor found in nearly all eukaryotic cells. When activated, AMPK inhibits anabolic pathways that consume ATP and activates catabolic processes that synthesize ATP. In this study, we overexpressed a truncated and constitutively active α-subunit of AMPK under the control of the midgut-specific carboxypeptidase promotor in the midgut of female Anopheles stephensi. As expected, AMPK overexpression in homozygous transgenic mosquitoes was associated with changes in nutrient storage and metabolism, decreasing glycogen levels at 24 h post-blood feeding when transgene expression was maximal, and concurrently increasing circulating trehalose at the same time point. When transgenic lines were challenged with Plasmodium falciparum, we observed a significant decrease in the prevalence and intensity of infection relative to wild type controls. Surprisingly, we did not observe a significant difference in the survival of adult mosquitoes fed either sugar only or both sugar and bloodmeals throughout adult life. This may be due to the limited period that the transgene was activated before homeostasis was restored. However, we did observe a significant decrease in egg production, suggesting that manipulation of AMPK activity in the mosquito midgut resulted in the re-allocation of resources away from egg production. In summary, this work identifies midgut AMPK activity as an important regulator of metabolism, reproduction, and innate immunity in An. stephensi, a highly invasive and important malaria vector species.
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影响因子：
12.8
作者：
Jeon SM
通讯作者：
Jeon SM
影响因子：
3.7
作者：
Kang SW;Haydar G;Taniane C;Farrell G;Arias IM;Lippincott-Schwartz J;Fu D
通讯作者：
Fu D
影响因子：
2.4
作者：
Horn, C;Wimmer, EA
通讯作者：
Wimmer, EA
影响因子：
6.7
作者：
Corby-Harris V;Drexler A;Watkins de Jong L;Antonova Y;Pakpour N;Ziegler R;Ramberg F;Lewis EE;Brown JM;Luckhart S;Riehle MA
通讯作者：
Riehle MA
DOI：
10.1073/pnas.0800478105
发表时间：
2008-04-15
影响因子：
11.1
作者：
Brown, Mark R.;Clark, Kevin D.;Strand, Michael R.
通讯作者：
Strand, Michael R.