Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells
Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells
复制标题
DOI：
10.1038/ng1658
复制
发表时间：
2005-11-01
期刊：
影响因子：
30.8
通讯作者：
Fleming, MD
中科院分区：
文献类型：
--
作者：
Ohgami, RS;Campagna, DR;Fleming, MD
铁的还原是转铁蛋白（Tf）循环中的重要步骤，转铁蛋白循环是红细胞前体吸收铁的主要途径。红细胞摄取铁的不足会导致低色素性小细胞性贫血。使用定位克隆策略，我们确定了一个基因，六跨膜上皮抗原的前列腺3（Steap3），负责缺铁性贫血的小鼠突变体nm1054。Steap3在造血组织中高度表达，与Tf循环内体共定位并促进Tf结合的铁摄取。Steap3与古细菌和细菌中发现的F420H2：NADP（+）氧化还原酶以及酵母FRE家族的金属还原酶具有同源性。Steap3的过表达刺激铁的还原，缺乏Steap3的小鼠缺乏红系铁还原酶活性。总之，这些发现表明，Steap3是一种内体铁还原酶，是红系细胞中有效的Tf依赖性铁摄取所必需的。
The reduction of iron is an essential step in the transferrin (Tf) cycle, which is the dominant pathway for iron uptake by red blood cell precursors. A deficiency in iron acquisition by red blood cells leads to hypochromic, microcytic anemia. Using a positional cloning strategy, we identified a gene, six-transmembrane epithelial antigen of the prostate 3 (Steap3), responsible for the iron deficiency anemia in the mouse mutant nm1054. Steap3 is expressed highly in hematopoietic tissues, colocalizes with the Tf cycle endosome and facilitates Tf-bound iron uptake. Steap3 shares homology with F420H2:NADP(+) oxidoreductases found in archaea and bacteria, as well as with the yeast FRE family of metalloreductases. Overexpression of Steap3 stimulates the reduction of iron, and mice lacking Steap3 are deficient in erythroid ferrireductase activity. Taken together, these findings indicate that Steap3 is an endosomal ferrireductase required for efficient Tf-dependent iron uptake in erythroid cells.