Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum
Open accessAbstract
In hereditary hemochromatosis (HH), intestinal absorption of dietary iron is increased, leading to excessive iron accumulation in tissues and resultant organ damage. The HFE protein, which is defective in HH, normally is expressed in crypt enterocytes of the duodenum where it has a unique, predominantly intracellular localization. In placenta, the HFE protein colocalizes with and forms a stable association with the transferrin receptor (TfR), providing a link between the HFE protein and iron transport. In the present study, we examined the relationship of the HFE protein to the TfR in enterocytes of the human duodenum and measured the uptake of transferrin-bound iron and ionic iron by isolated crypt and villus enterocytes. Immunocytochemistry showed that the HFE protein and TfR both are expressed in the crypt enterocytes. Western blots showed that, as was the case in human placenta, the HFE protein in crypt enterocytes is physically associated with the TfR and with β 2 -microglobulin. The crypt cell fraction exhibited dramatically higher transferrin-bound iron uptake than villus cells. On the other hand, the villus cells showed 2–3 times higher uptake of ionic iron than crypt cells. We propose that the HFE protein modulates the uptake of transferrin-bound iron from plasma by crypt enterocytes and participates in the mechanism by which the crypt enterocytes sense the level of body iron stores. Impairment of this function caused by HFE gene mutations in HH could provide a paradoxical signal in crypt enterocytes that programs the differentiating enterocytes to absorb more dietary iron when they mature into villus enterocytes.
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TfR2 has a lower affinity for Fe-Tf than does TfR1.
“TfR2 has a lower affinity for Fe-Tf than does TfR1 (160, 320).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [320]
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Research works printed but not linked: 7
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- Authors
- Waheed, A., Parkkila, S., Saarnio, J., Fleming, R. E., Zhou, X. Y., Tomatsu, S., Britton, R. S., Bacon, B. R., & Sly, W. S.
- Affiliations
- Edward A. Doisy Department of Biochemistry and Molecular Biology, Department of Pediatrics, and Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104; and Department of Surgery, University of Oulu, Oulu, Finland 90220
- Saint Louis University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-02-16
- Volume
- 96
- Issue
- 4
- Pages
- 1579-1584
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC15523
- OpenAlex
- W2091028002
- Cited by
- 243
- References
- 38
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 1 · 2021: 2 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 2 · 2012: 5
- FWCI
- 19.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM34182, R01GM034182)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 53405, R01DK041816, R01DK053405, DK-40163, R01DK040163)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- transferrin receptor, hereditary hemochromatosis, intestinal iron absorption, beta2-microglobulin, iron homeostasis, HFE gene mutations
- MeSH terms
- Hemochromatosis Protein, beta 2-Microglobulin, Biological Transport, Duodenum, Hemochromatosis, HLA Antigens, Humans, Immunohistochemistry, Intestinal Mucosa, Iron, Iron Radioisotopes, Membrane Proteins, Receptors, Transferrin, Histocompatibility Antigens Class I
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