IRON TRANSPORTER-FUNCTIONAL CHARACTERIZATION--REGULATION

铁是所有物种必需的微量元素。它被利用了 由所有细胞组成，在许多蛋白质中是一个重要的辅因子。 然而，如果它积累过多，它可以催化 形成危险的有机和氧基有毒自由基。 因此，这种自由过渡金属在 生物体液受到严格控制。在肠道中， 抗坏血酸等还原剂，以及酶的活性 铁还原酶增强铁的吸收，使铁 通过Fe2+专属的转运系统进入肠道细胞。 尽管有广泛的研究，但肠道铁的分子机制 吸收仍不清楚，Fe2+转运体还没有被发现 哺乳动物的报告。在Hediger博士(我的实验室)工作 赞助商)，我最近成功地克隆了一个Fe2+ 转运蛋白(IDCTl，铁首选二价阳离子转运蛋白L) 利用非洲爪哇表达克隆缺铁大鼠十二指肠组织 卵母细胞。这项提案的目标是描述这一点 转运蛋白(L)阐明其结构与功能 IDCT1的关系，2)确定细胞和亚细胞 免疫细胞化学定位IDCT1在不同组织中的分布 3)研究IDCTI基因的表达调控。我也是 建议克隆一个假定的低亲和力铁转运蛋白，AS 和锌一样。

Iron is an essential trace element for all species. It is utilized by all cells and represents an important cofactor in many proteins. Yet, if it accumulates in excessive amounts, it can catalyze the formation of dangerous organic and oxygen-based toxic radicals. Therefore, the concentration of this free transition metal in biological fluids is under tight control. In the intestine, reductants such as ascorbic acid, as well as the activity of ferrireductase enhance iron absorption, allowing iron to be transported into enterocytes via a Fe2+-specific transport system. Despite extensive studies, molecular mechanisms of intestinal iron absorption remain unknown, and an Fe2+ transporter has not yet been reported for mammals. Working in the laboratory of Dr. Hediger (my sponsor), I have recently been successful in cloning an Fe2+ transporter (IDCTl, Iron preferring Divalent Cation Transporter l) from iron deficient rat duodenum by expression cloning with Xenopus oocytes. The goal of this proposal is to characterize this transporter protein by l) elucidating the structure-function relationship of IDCTl, 2) determining the cellular and subcellular localization of IDCTl in various tissues using immunocytochemistry, and 3) investigating the regulation of IDCTI mRNA. I am also proposing to clone a putative low affinity iron transporter, as well as a zinc.