title: Roles of transferrin receptors in erythropoiesis.
abstract: Erythropoiesis requires large amounts of iron for hemoglobin synthesis, which is mainly provided by macrophages and the intestines in a transferrin (Tf)-bound form. Bone marrow erythroblasts incorporate Tf through endocytosis, which is mediated by transferrin receptor 1 (TFR1). Recently, human TFR1, aside from its role as a Tf receptor, was also found to be a receptor for the H-subunit of ferritin (FTH). In humans, hematopoietic erythroid precursor cells express high levels of TFR1 and specifically take up the FTH homopolymer (H-ferritin). H-ferritin inhibits the formation of burst forming unit-erythroid colonies in vitro. TFR2, which is also a Tf receptor, is predominantly expressed in hepatocytes and erythroid precursor cells. In the liver, TFR2 forms a complex with HFE, a hereditary hemochromatosis-associated protein, and acts as an iron sensor. In mice, hepatocyte-specific knockout of the TFR2 gene has been shown to cause systemic iron-overload with decreased expression of hepcidin, the central regulator of iron homeostasis. In erythroid cells, TFR2 forms a complex with the erythropoietin receptor and facilitates its trafficking to the cell membrane. Moreover, hematopoietic cell-specific knockout of the TFR2 gene causes microcytic erythrocytosis in mice. This review focuses on the molecular evolution and functions of these TFRs and their ligands.
authors: Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University.
authors: Hiroshi
authors: H
authors: Kawabata
authors: Soichiro
authors: S
authors: Sakamoto
authors: Taro
authors: T
authors: Masuda
authors: Tatsuki
authors: T
authors: Uchiyama
authors: Katsuyuki
authors: K
authors: Ohmori
authors: H Phillip
authors: HP
authors: Koeffler
authors: Akifumi
authors: A
authors: Takaori-Kondo
mesh_terms: D000818:Animals; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis; D019143:Evolution, Molecular; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*
chemical_list: D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron