Analyses for binding of the transferrin family of proteins to the transferrin receptor 2

• Published in: British journal of haematology Vol. 127; no. 4; pp. 464 - 473
• Main Authors: Kawabata, Hiroshi, Tong, Xiangjun, Kawanami, Takafumi, Wano, Yuji, Hirose, Yuko, Sugai, Susumu, Phillip Koeffler, H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.11.2004; Blackwell; Blackwell Publishing Ltd
• Subjects: Biological and medical sciences; Biotinylation; Blotting, Western; Cells, Cultured; Flow Cytometry; functional studies; Hematologic and hematopoietic diseases; Hematology; Humans; iron; iron metabolism; iron overload; Medical sciences; Mutation - genetics; Receptors, Transferrin - genetics; Receptors, Transferrin - metabolism; Transferrin - genetics; Transferrin - metabolism; iron metabolism; iron overload; Transferrin; functional studies; Hematology; Overload; Iron; Metabolism; Transferrin receptor 2; Protein
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2004.05224.x

Summary Transferrin receptor 2α (TfR2α), the major product of the TfR2 gene, is the second receptor for transferrin (Tf), which can mediate cellular iron uptake in vitro. Homozygous mutations of TfR2 cause haemochromatosis, suggesting that TfR2α may not be a simple iron transporter, but a regulator of iron by identifying iron‐Tf. In this study, we analysed the ligand specificity of TfR2α using human transferrin receptor 1 (TfR1) and TfR2α‐stably transfected and expressing cells and flow‐cytometric techniques. We showed that human TfR2α interacted with both human and bovine Tf, whereas human TfR1 interacted only with human Tf. Neither human TfR1 nor TfR2α interacted with either lactoferrin or melanotransferrin. In addition, by creating point mutations in human TfR2α, the RGD sequence in the extracellular domain of TfR2α was shown to be crucial for Tf‐binding. Furthermore, we demonstrated that mutated TfR2α (Y250X), which has been reported in patients with hereditary haemochromatosis, also lost its ability to interact with both human and bovine Tf. Although human TfR1 and TfR2α share an essential structure (RGD) for ligand‐binding, they have clearly different ligand specificities, which may be related to the differences in their roles in iron metabolism.