Arik Anam J, Hun Lewis V, Quicke Kendra, Piatt Michael, Ziegler Rolf, Scaraffia Patricia Y, Badgandi Hemant, Riehle Michael A
*Department of Entomology, University of Arizona, Tucson, Arizona, USA; Department of Pediatrics, Emory University, Atlanta, Georgia, USA; Department of Tropical Medicine, Vector-Borne Infectious Diseases Research Center, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA; and Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
*Department of Entomology, University of Arizona, Tucson, Arizona, USA; Department of Pediatrics, Emory University, Atlanta, Georgia, USA; Department of Tropical Medicine, Vector-Borne Infectious Diseases Research Center, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA; and Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
FASEB J. 2015 Apr;29(4):1404-13. doi: 10.1096/fj.14-261479. Epub 2014 Dec 30.
Akt signaling regulates diverse physiologies in a wide range of organisms. We examine the impact of increased Akt signaling in the fat body of 2 mosquito species, the Asian malaria mosquito Anopheles stephensi and the yellow fever mosquito Aedes aegypti. Overexpression of a myristoylated and active form of A. stephensi and Ae. aegypti Akt in the fat body of transgenic mosquitoes led to activation of the downstream signaling molecules forkhead box O (FOXO) and p70 S6 kinase in a tissue and blood meal-specific manner. In both species, increased Akt signaling in the fat body after blood feeding significantly increased adult survivorship relative to nontransgenic sibling controls. In A. stephensi, survivorship was increased by 15% to 45%, while in Ae. aegypti, it increased 14% to 47%. Transgenic mosquitoes fed only sugar, and thus not expressing active Akt, had no significant difference in survivorship relative to nontransgenic siblings. Expression of active Akt also increased expression of fat body vitellogenin, but the number of viable eggs did not differ significantly between transgenic and nontransgenic controls. This work demonstrates a novel mechanism of enhanced survivorship through increased Akt signaling in the fat bodies of multiple mosquito genera and provides new tools to unlock the molecular underpinnings of aging in eukaryotic organisms.
Akt信号传导调节多种生物体中的多种生理过程。我们研究了增加Akt信号传导对两种蚊子——亚洲疟疾蚊子斯氏按蚊和黄热病蚊子埃及伊蚊脂肪体的影响。在转基因蚊子的脂肪体中过表达肉豆蔻酰化的活性形式的斯氏按蚊和埃及伊蚊Akt，导致下游信号分子叉头框O（FOXO）和p70 S6激酶以组织和血餐特异性方式被激活。在这两个物种中，与非转基因同胞对照相比，吸血后脂肪体中Akt信号传导增加显著提高了成虫的存活率。在斯氏按蚊中，存活率提高了15%至45%，而在埃及伊蚊中，提高了14%至47%。仅喂食糖且因此不表达活性Akt的转基因蚊子，其存活率与非转基因同胞相比没有显著差异。活性Akt的表达也增加了脂肪体卵黄蛋白原的表达，但转基因和非转基因对照之间的可存活卵数量没有显著差异。这项工作证明了通过增加多种蚊子属脂肪体中的Akt信号传导来提高存活率的新机制，并提供了新工具来揭示真核生物衰老的分子基础。
