Heterotypic interactions between transferrin receptor and transferrin receptor 2.
Cellular iron uptake in most tissues occurs via endocytosis of diferric transferrin (Tf) bound to the transferrin receptor (TfR). Recently, a second transferrin receptor, transferrin receptor 2 (TfR2), has been identified and shown to play a critical role in iron metabolism. TfR2 is capable of Tf-mediated iron uptake and mutations in this gene result in a rare form of hereditary hemochromatosis unrelated to the hereditary hemochromatosis protein, HFE. Unlike TfR, TfR2 expression is not controlled by cellular iron concentrations and little information is currently available regarding the role of TfR2 in cellular iron homeostasis. To investigate the relationship between TfR and TfR2, we performed a series of in vivo and in vitro experiments using antibodies generated to each receptor. Western blots demonstrate that TfR2 protein is expressed strongest in erythroid/myeloid cell lines. Metabolic labeling studies indicate that TfR2 protein levels are approximately 20-fold lower than TfR in these cells. TfR and TfR2 have similar cellular localizations in K562 cells and coimmunoprecipitate to only a very limited extent. Western analysis of the receptors under nonreducing conditions reveals that they can form heterodimers.
Vogt
Todd M
TM
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland OR 97201-3098, USA.
Blackwell
Aaron D
AD
Giannetti
Anthony M
AM
Bjorkman
Pamela J
PJ
Enns
Caroline A
CA
D000595:Amino Acid Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D003545:Cysteine / Q000737:chemistry; D003553:Cystine / Q000737:chemistry; D019281:Dimerization; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D020014:K562 Cells / Q000378:metabolism / Q000648:ultrastructure; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry; D010084:Oxidation-Reduction; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000737:chemistry; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000648:ultrastructure
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D003553:Cystine; D003545:Cysteine