HFE association with transferrin receptor 2 increases cellular uptake of transferrin-bound iron |
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Authors: | Waheed Abdul Britton Robert S Grubb Jeffrey H Sly William S Fleming Robert E |
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Institution: | a Edward A. Doisy Department of Biochemistry & Molecular Biology, Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, MO 63104, USA b Department of Internal Medicine, Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, MO 63104, USA c Department of Pediatrics, Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, MO 63104, USA |
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Abstract: | Mutations in either HFE or transferrin receptor 2 (TfR2) cause decreased expression of the iron regulatory hormone hepcidin and hemochromatosis. HFE and TfR2 were recently discovered to form a stable complex at the cell membrane when co-expressed in heterologous cell lines. We analyzed the functional consequences of the co-expression of these proteins using transfected TRVb cells, a Chinese hamster ovary derived cell line without endogenous HFE or transferrin receptor. The co-expression of TfR2 in TRVb cells expressing HFE led to accelerated HFE biosynthesis and late-Golgi maturation, suggesting interaction prior to cell surface localization. The co-expression of HFE in cells expressing TfR2 led to increased affinity for diferric transferrin, increased transferrin-dependent iron uptake, and relative resistance to iron chelation. These observations indicate that HFE influences the functional properties of TfR2, and suggests a model in which the interaction of these proteins might influence signal transduction to hepcidin. |
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Keywords: | Endocytosis Ferritin Hemochromatosis Hepcidin TRVb cells |
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