Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa-ken 920-0293, Japan.
Free Radic Biol Med. 2019 Mar;133:46-54. doi: 10.1016/j.freeradbiomed.2018.06.037. Epub 2018 Jun 30.
In vertebrates, transferrin (Tf) safely delivers iron through circulation to cells. Tf-bound iron is incorporated through Tf receptor (TfR) 1-mediated endocytosis. TfR1 can mediate cellular uptake of both Tf and H-ferritin, an iron storage protein. New World arenaviruses, which cause hemorrhagic fever, and Plasmodium vivax use TfR1 for entry into host cells. Human TfR2, another receptor for Tf, is predominantly expressed in hepatocytes and erythroid precursors, and holo-Tf dramatically upregulates its expression. TfR2 forms a complex with hemochromatosis protein, HFE, and serves as a component of the iron sensing machinery in hepatocytes. Defects in TfR2 cause systemic iron overload, hemochromatosis, through down-regulation of hepcidin. In erythroid cells, TfR2 forms a complex with the erythropoietin receptor and regulates erythropoiesis. TfR2 facilitates iron transport from lysosomes to mitochondria in erythroblasts and dopaminergic neurons. Administration of apo-Tf, which scavenges free iron, has been explored for various clinical conditions including atransferrinemia, iron overload, and tissue ischemia. Apo-Tf has also been shown to ameliorate anemia in animal models of β-thalassemia. In this review, I provide an update and summary on our knowledge of mammalian Tf and its receptors.
在脊椎动物中，转铁蛋白 (Tf) 通过循环将铁安全地输送到细胞中。Tf 结合的铁通过 Tf 受体 (TfR)1 介导的内吞作用被摄取。TfR1 可以介导 Tf 和铁蛋白（一种铁储存蛋白）的细胞摄取。引起出血热的新世界沙粒病毒和间日疟原虫利用 TfR1 进入宿主细胞。人类 TfR2 是 Tf 的另一种受体，主要在肝细胞和红细胞前体中表达，并且完整 Tf 可显著上调其表达。TfR2 与血色病蛋白 HFE 形成复合物，作为肝细胞中铁感应机制的组成部分。TfR2 的缺陷通过下调铁调素导致全身性铁过载和血色病。在红细胞中，TfR2 与促红细胞生成素受体形成复合物并调节红细胞生成。TfR2 促进从溶酶体向红细胞和成多巴胺神经元中的线粒体转运铁。已探索用脱铁转铁蛋白（可清除游离铁）来治疗各种临床病症，包括转铁蛋白血症、铁过载和组织缺血。脱铁转铁蛋白还被证明可改善β-地中海贫血动物模型中的贫血。在这篇综述中，我提供了关于哺乳动物 Tf 及其受体的最新知识总结。
