Characterization of a reproductive hormone receptor from mosquitoes

描述（由申请人提供）：与所有动物一样，蚊子的繁殖是一个受到严格调控的过程，涉及多种生理事件的协调，包括营养吸收和卵子成熟。在吸血后大脑释放的神经肽卵巢卵巢甾体生成激素（OEH）已被证明是蚊子繁殖的主要调节器。OEH与胰岛素样肽（ILPs）协同作用，刺激蚊子卵巢释放表皮类固醇，从而刺激导致卵群成熟的事件。从吸血蚊子身上剥夺OEH完全阻止了蚊子的繁殖，这是破坏策略的一个有希望的目标。与ILPs不同的是，OEH缺乏一种特征性的受体，并且由OEH触发并导致表皮甾体释放的信号通路尚不清楚。利用比较基因组学和功能方法，我在埃及伊蚊中发现了一种候选OEH受体，命名为R1915。为了阐明R1915在OEH信号传导中的作用，我提出了以下3个目标：1)生物化学证实R1915是OEH受体并充分评估受体的时空表达；2)表征OEH的信号通路；3)评估OEH和R1915如何影响生殖过程，包括血粉消化和卵巢成熟。这项研究的结果将提供对蚊子繁殖调控的见解，为阻断蚊子媒介疾病传播的策略提供新的靶点。

DESCRIPTION (provided by applicant): Reproduction in mosquitoes, like all animals, is a tightly regulated process that involves coordination of several physiological events including nutrient uptake and egg maturation. The neuropeptide ovary ecdysteroidogenic hormone (OEH) - released from the brain after a bloodmeal - has been demonstrated to be a master regulator of reproduction in mosquitoes. In concert with insulin-like peptides (ILPs), OEH stimulates the release of ecdysteroids from the mosquito ovaries, which then stimulate events leading to the maturation of an egg clutch. Deprivation of OEH from bloodfed mosquitoes completely arrests reproduction, and is a promising target for disruption strategies. Unlike ILPs, OEH lacks a characterized receptor and the signaling pathway triggered by OEH and leading to ecdysteroid release is unknown. Utilizing a comparative genomics and functional approach, I have identified a candidate OEH receptor in Aedes aegypti named R1915. To elucidate the role of R1915 in OEH signaling, I propose the following 3 aims: 1) biochemically confirm R1915 is the OEH receptor and fully assess spatiotemporal expression of the receptor, 2) characterize the signaling pathway of OEH, and 3) assess how OEH and R1915 influence reproductive processes including bloodmeal digestion and ovary maturation. The results of this research will provide insights into the regulation of reproduction in mosquitoes, providing new targets for strategies to disrupt mosquito-vectored disease transmission.