Programmed autophagy in the fat body of Aedes aegypti is required to maintain egg maturation cycles.
Programmed autophagy in the fat body of Aedes aegypti is required to maintain egg maturation cycles.
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DOI：
10.1371/journal.pone.0025502
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Raikhel AS
中科院分区：
文献类型：
--
作者：
Bryant B;Raikhel AS
在压力、饥饿、发育和癌症等条件下，细胞自噬起着关键作用，允许细胞回收细胞成分。在这项工作中，我们已经证明了蚊子脂肪体中的程序性自噬在维持促性腺激素周期正常进展所需的发育开关中起着关键作用。蚊子必须以脊椎动物的血液为食才能产卵，每个促性腺激素周期都与单独的血液紧密相连。因此，一些蚊子是病原体的载体，在人类和家畜中引起毁灭性疾病，最重要的是疟疾和登革热。因此，破译控制卵子发育周期的机制对于设计控制蚊子的新方法至关重要。卵子发育的核心是卵黄形成，卵黄蛋白前体在脂肪体中的产生，类似于脊椎动物肝脏的组织，以及它们随后在发育中的卵母细胞中的特异性积累。在每个卵子发育周期中，脂肪体经历了一个发育过程，包括卵黄形成前生物合成机制的建立、卵黄蛋白前体的强烈产生和卵黄形成的终止。一些自噬基因（ATGs）的RNA干扰（RNAi）耗尽，抑制了自噬，导致TOR过早过度激活，延长了主要卵黄蛋白前体卵黄原蛋白（Vg）的产生，证实了自噬对卵黄形成终止的重要性。脱皮激素受体（EcR）的RNAi耗竭证明了其激活自噬的作用。自噬基因和EcR的缺失导致能力因子betaFTZ-F1的抑制，这是蜕皮激素介导的发育转变所必需的。此外，自噬能力不足的雌蚊无法完成第二次生殖周期，卵成熟发育迟缓和异常。因此，我们的研究揭示了程序性自噬在维持蚊子卵成熟周期中的新功能。
Autophagy plays a pivotal role by allowing cells to recycle cellular components under conditions of stress, starvation, development and cancer. In this work, we have demonstrated that programmed autophagy in the mosquito fat body plays a critical role in maintaining of developmental switches required for normal progression of gonadotrophic cycles. Mosquitoes must feed on vertebrate blood for their egg development, with each gonadotrophic cycle being tightly coupled to a separate blood meal. As a consequence, some mosquito species are vectors of pathogens that cause devastating diseases in humans and domestic animals, most importantly malaria and Dengue fever. Hence, deciphering mechanisms to control egg developmental cycles is of paramount importance for devising novel approaches for mosquito control. Central to egg development is vitellogenesis, the production of yolk protein precursors in the fat body, the tissue analogous to a vertebrate liver, and their subsequent specific accumulation in developing oocytes. During each egg developmental cycle, the fat body undergoes a developmental program that includes previtellogenic build-up of biosynthetic machinery, intense production of yolk protein precursors, and termination of vitellogenesis. The importance of autophagy for termination of vitellogenesis was confirmed by RNA interference (RNAi) depletions of several autophagic genes (ATGs), which inhibited autophagy and resulted in untimely hyper activation of TOR and prolonged production of the major yolk protein precursor, vitellogenin (Vg). RNAi depletion of the ecdysone receptor (EcR) demonstrated its activating role of autophagy. Depletion of the autophagic genes and of EcR led to inhibition of the competence factor, betaFTZ-F1, which is required for ecdysone-mediated developmental transitions. Moreover, autophagy-incompetent female mosquitoes were unable to complete the second reproductive cycle and exhibited retardation and abnormalities in egg maturation. Thus, our study has revealed a novel function of programmed autophagy in maintaining egg maturation cycles in mosquitoes.
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DOI：
10.1016/j.bbamcr.2009.02.009
发表时间：
2009-09
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
McPhee CK;Baehrecke EH
通讯作者：
Baehrecke EH
酵母突变体在细胞质中的分离和表征与液泡蛋白靶向途径的分离。
影响因子：
7.8
作者：
HARDING, TM;MORANO, KA;SCOTT, SV;KLIONSKY, DJ
通讯作者：
KLIONSKY, DJ
DOI：
10.1126/science.1193162
发表时间：
2010-10-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bartholomay LC;Waterhouse RM;Mayhew GF;Campbell CL;Michel K;Zou Z;Ramirez JL;Das S;Alvarez K;Arensburger P;Bryant B;Chapman SB;Dong Y;Erickson SM;Karunaratne SH;Kokoza V;Kodira CD;Pignatelli P;Shin SW;Vanlandingham DL;Atkinson PW;Birren B;Christophides GK;Clem RJ;Hemingway J;Higgs S;Megy K;Ranson H;Zdobnov EM;Raikhel AS;Christensen BM;Dimopoulos G;Muskavitch MA
通讯作者：
Muskavitch MA
影响因子：
4.8
作者：
Brown, MR;Graf, R;Lea, AO
通讯作者：
Lea, AO
影响因子：
3.5
作者：
Chen, L;Zhu, J;Raikhel, AS
通讯作者：
Raikhel, AS