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Cited by 451Iron Metabolism and DisordersTrace Elements in HealthPlant Micronutrient Interactions and Effects

Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron.

Canonne-Hergaux, F., Gruenheid, S., Ponka, P., Gros, P.·1999·Blood
DOI 10.1182/blood.v93.12.4406
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Abstract

Genetic studies in animal models of microcytic anemia and biochemical studies of transport have implicated the Nramp2 gene in iron transport. Nramp2 generates two alternatively spliced mRNAs that differ at their 3' untranslated region by the presence or absence of an iron-response element (IRE) and that encode two proteins with distinct carboxy termini. Antisera raised against Nramp2 fusion proteins containing either the carboxy or amino termini of Nramp2 and that can help distinguish between the two Nramp2 protein isoforms (IRE: isoform I; non-IRE: isoform II) were generated. These antibodies were used to identify the cellular and subcellular localization of Nramp2 in normal tissues and to study possible regulation by dietary iron deprivation. Immunoblotting experiments with membrane fractions from intact organs show that Nramp2 is expressed at low levels throughout the small intestine and to a higher extent in kidney. Dietary iron starvation results in a dramatic upregulation of the Nramp2 isoform I in the proximal portion of the duodenum only, whereas expression in the rest of the small intestine and in kidney remains largely unchanged in response to the lack of dietary iron. In proximal duodenum, immunostaining studies of tissue sections show that Nramp2 protein expression is abundant under iron deplete condition and limited to the villi and is absent in the crypts. In the villi, staining is limited to the columnar absorptive epithelium of the mucosa (enterocytes), with no expression in mucus-secreting goblet cells or in the lamina propria. Nramp2 expression is strongest in the apical two thirds of the villi and is very intense at the brush border of the apical pole of the enterocytes, whereas the basolateral membrane of these cells is negative for Nramp2. These results strongly suggest that Nramp2 is indeed responsible for transferrin-independent iron uptake in the duodenum. These findings are discussed in the context of overall mechanisms of iron acquisition by the body.

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  • Intestinal DMT1 is primarily localized to the apical membrane and to subapical endosomes.

    “Intestinal DMT1 is primarily localized to the apical membrane and to subapical endosomes.59”

    From Forging a field: the golden age of iron biology. (2008) · cites this paper as [59]

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Authors
Canonne-Hergaux, F., Gruenheid, S., Ponka, P., & Gros, P.
Affiliations
  • From the Departments of Biochemistry and Physiology, McGill University, Montreal, Quebec, Canada; and the Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
  • Jewish General Hospital (CA)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
1999-06-15
Volume
93
Issue
12
Pages
4406-4417
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v93.12.4406
OpenAlex
W130498243
Cited by
451
References
81
Citations by year
2026: 1 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 9 · 2021: 14 · 2020: 7 · 2019: 9 · 2018: 12 · 2017: 15 · 2016: 7 · 2015: 11 · 2014: 18 · 2013: 15 · 2012: 16
FWCI
16.36
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Allergy and Infectious Diseases (AI-35237)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
Keywords
DMT1, iron transporters, intestinal iron absorption, brush border, duodenum, iron-responsive element, alternative splicing, protein isoforms, enterocytes, subcellular localization, microcytic anemia, iron acquisition
MeSH terms
Natural Resistance-associated Macrophage Protein 1, Solute Carrier Family 11, Member 2, Animals, Antibody Specificity, Carrier Proteins, Duodenum, Cricetinae, Immune Sera, Immunohistochemistry, Intestines, Iron, Membrane Proteins, Mice, Inbred Strains, Microvilli, RNA, Messenger, Tissue Distribution, Transfection, Immunoblotting, CHO Cells, Alternative Splicing, Iron, Dietary, Cation Transport Proteins, Iron-Binding Proteins, Mice

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