ArticleProceedings of the National Academy of Sciences of the United States of America1997
Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 345 citations in OpenAlex.
- Advance in placenta drug delivery: concern for placenta-originated disease therapy.Drug delivery · 2023Review
- Iron transport kinetics through blood-brain barrier endothelial cells.Biochimica et biophysica acta. General subjects · 2018Article
- What can we learn from ineffective erythropoiesis in thalassemia?Blood reviews · 2018Review
- The Effects ofIndian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2017Article
- The role of MHC class Ib-restricted T cells during infection.Immunogenetics · 2016Review
- Iron uptake and transport across physiological barriers.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2016Review
- Human Hemochromatosis Protein (HFE) Immunoperoxidase Stain Highlights Choriocarcinoma within Mixed Germ Cell Tumors.Disease markers · 2016Article
- Review
- Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study.Environmental health : a global access science source · 2014Article
- Role of duodenal iron transporters and hepcidin in patients with alcoholic liver disease.Journal of cellular and molecular medicine · 2014Article
- Molecular insights into the regulation of iron metabolism during the prenatal and early postnatal periods.Cellular and molecular life sciences : CMLS · 2013Review
- In situ proximity ligation assays indicate that hemochromatosis proteins Hfe and transferrin receptor 2 (Tfr2) do not interact.PloS one · 2013Article
- Duodenal expression of iron transport molecules in patients with hereditary hemochromatosis or iron deficiency.Journal of cellular and molecular medicine · 2012Article
- Fetal iron levels are regulated by maternal and fetal Hfe genotype and dietary iron.Haematologica · 2012Article
- Ubiquitination of lysine-331 by Kaposi's sarcoma-associated herpesvirus protein K5 targets HFE for lysosomal degradation.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- HFE gene variants modify the association between maternal lead burden and infant birthweight: a prospective birth cohort study in Mexico City, Mexico.Environmental health : a global access science source · 2010Article
- Stoichiometries of transferrin receptors 1 and 2 in human liver.Blood cells, molecules & diseases · 2010Article
- Bone morphogenetic protein signaling is impaired in an HFE knockout mouse model of hemochromatosis.Gastroenterology · 2009Article
- Forging a field: the golden age of iron biology.Blood · 2008Review
- Viral infection and iron metabolism.Nature reviews. Microbiology · 2008Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hereditary hemochromatosis (HH) is a common autosomal recessive disease associated with loss of regulation of dietary iron absorption and excessive iron deposition in major organs of the body. Recently, a candidate gene for HH (also called HFE) was identified that encodes a novel MHC class I-like protein. Most patients with HH are homozygous for the same mutation in the HFE gene, resulting in a C282Y change in the HFE protein. Studies in cultured cells show that the C282Y mutation abrogates the binding of the recombinant HFE protein to beta2-microglobulin (beta2M) and disrupts its transport to the cell surface. The HFE protein was shown by immunohistochemistry to be expressed in certain epithelial cells throughout the human alimentary tract and to have a unique localization in the cryptal cells of small intestine, where signals to regulate iron absorption are received from the body. In the studies presented here, we demonstrate by immunohistochemistry that the HFE protein is expressed in human placenta in the apical plasma membrane of the syncytiotrophoblasts, where the transferrin-bound iron is normally transported to the fetus via receptor-mediated endocytosis. Western blot analyses show that the HFE protein is associated with beta2M in placental membranes. Unexpectedly, the transferrin receptor was also found to be associated with the HFE protein/beta2M complex. These studies place the normal HFE protein at the site of contact with the maternal circulation where its association with transferrin receptor raises the possibility that the HFE protein plays some role in determining maternal/fetal iron homeostasis. These findings also raise the question of whether mutations in the HFE gene can disrupt this association and thereby contribute to some forms of neonatal iron overload.
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