转铁蛋白 Tsfs 在果蝇铁代谢中的调控作用及机制研究

转铁蛋白（transferrin,Tsf）是哺乳动物执行铁摄取和转运的重要蛋白，果蝇中存在三个Tsfs同源基因Tsf1、Tsf2和Tsf3，但它们在铁吸收及平衡维持中功能尚不清楚。我们的初步实验表明，Tsf1和Tsf2对果蝇生长发育是必需的。金属敏感性分析显示，Tsf1在果蝇体内铁代谢中具有重要作用。进一步分析发现，Tsf1极有可能参与果蝇肠铁吸收过程。本项目拟在前期工作基础上系统研究Tsfs功能，阐明其参与铁代谢的分子机制，寻找上游供体和下游受体；探究不同组织合成的Tsfs功能；通过探究Tsfs与已鉴定铁吸收过程发挥重要功能的ferritin、dZIP13的关系阐明果蝇肠铁吸收机制；鉴定果蝇储铁器官及储铁机制。期望本项目的实施能阐明果蝇Tsfs功能，揭示机体系统水平的铁吸收和存储机制，大大推进果蝇铁代谢发展，为铁代谢及与疾病之间的关系的研究提供理论基础和技术途径。

Transferrin is the transporter responsible for iron delivery in mammalian, it is the main way for tissues and systemically iron absorption. There are three homologs in drosophila, Tsf1 Tsf2 and Tsf3, but their function in iron metabolism remains unclear. In order to identify their function, we performed some experiments. The results indicated that Tsf1 and Tsf2 are required for development. Systemic Tsf1 knockdown led to reduced eclosion rate and shorten lifespan, systemic Tsf2 knockdown resulted in embryonic lethality and systemic Tsf3 knockdown had no obvious abnormalities. Tsf1 RNAi was more sensitive to iron defeciency and Tsf1 OE was more sensitive to iron overload, iron loaded in ferritin was induced in Tsf1 RNAi and reduced in Tsf1 OE, indicating that Tsf1 is participate in iron metabolism. We propose to achieve the functional identification of drosophila transferrin from molecular level to systemical level . The results are expetected to fill the knowledge gap in iron metabolism of drosophila, provide a reference for iron study in mammals including humans and lay the foundation for future research on the relationship between iron metabolism and disease.