Cationic Amino Acid Transport in Mosquitoes

描述（由申请人提供）：项目摘要/摘要拟议研究的主要目标是黄热病蚊子埃及伊蚊（登革热的主要载体）脂肪体中阳离子氨基酸（AA）易位系统的分子表征。为了适应其独特的生活方式，成年蚊子的脂肪组织中含有一个AA传感和运输系统，这是繁殖所必需的。蚊子的营养状况会影响这一系统。蚊子吸血后脂肪体质膜上阳离子氨基酸的运输是蚊子繁殖所必需的。在脊椎动物中，阳离子AA被溶质载体家族7（SLC 7）的蛋白质易位。我们已经确定了SLC 7家族的转运蛋白作为转运蛋白的阳离子AA L-组氨酸在蚊子，但是，还没有全面的调查到目前为止的其他阳离子AA的运输机制。因此，阳离子AA转运蛋白，其底物特异性和运输动力学尚未确定。为了解决这个问题，我们将使用焦磷酸测序，反向遗传学和电生理技术的组合。拟议的工作将实现一个显着的知识增益在该领域的AA运输媒介蚊子。. 公共卫生相关性：拟议的工作将证明通过识别和表征基本的和蚊子/昆虫特异性的转运蛋白对人类健康具有重要意义，这些转运蛋白为开发杀虫物质提供了高价值的目标。

DESCRIPTION (provided by applicant): Project Summary/Abstract The main goal of the proposed study is the molecular characterization of the cationic amino acid (AA) translocation system in the fat body of the Yellow fever mosquito Aedes aegypti, the principle vector for Dengue fever. As an adaption to their unique life style, the fat body tissue of adult mosquitoes houses an AA sensing and transport system which is essential for reproduction. The nutritional status of mosquitoes affects this system. The transport of cationic AAs over the fat body plasma membrane after a blood meal is indispensable for mosquito reproduction. In vertebrates cationic AAs are translocated by proteins of the Solute Carrier Family 7 (SLC7). We have identified one transporter of the SLC7 family as a transporter for the cationic AA L-histidine in mosquitoes; however, there has been no comprehensive investigation into the transport mechanisms of the other cationic AAs so far. Consequently, cationic AA transporters, their substrate specificities, and transport kinetics have not been identified. To address this problem we will use a combination of pyrosequencing, reverse genetics, and electrophysiological techniques. The proposed work will achieve a significant gain of knowledge in the field of AA transport in vector mosquitoes. . PUBLIC HEALTH RELEVANCE: Project Narrative The proposed work will prove significant for human health through the identification and characterization of essential and mosquito/insect-specific transporters that present high-value targets for the development of insecticidal substances.