Characterization of a reproductive hormone receptor from mosquitoes

描述(申请人提供)：蚊子的繁殖，像所有动物一样，是一个严格调控的过程，涉及几个生理事件的协调，包括营养吸收和卵子成熟。神经肽卵巢蜕皮激素(OEH)--一餐血后从大脑释放出来的--已被证明是蚊子繁殖的主要调节因素。在胰岛素样多肽(ILPS)的共同作用下，OEH刺激蚊子卵巢释放蜕皮类固醇，然后刺激导致卵窝成熟的事件。从吸血的蚊子身上剥夺OEH完全阻止了生殖，这是一个有希望的干扰策略的目标。与ILPS不同，OEH缺乏特征性的受体，OEH触发并导致蜕皮类固醇释放的信号通路尚不清楚。利用比较基因组学和功能方法，我已经在埃及伊蚊中确定了一个候选的OEH受体，命名为R1915。为了阐明R1915在OEH信号转导中的作用，我提出了以下3个目标：1)生化确认R1915是OEH受体，并全面评估该受体的时空表达；2)表征OEH的信号通路；3)评估OEH和R1915如何影响生殖过程，包括血液消化和卵巢成熟。这项研究的结果将为蚊子繁殖的调控提供洞察力，为阻断蚊媒疾病传播的战略提供新的目标。

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.