The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Alternative Splicing Regulates the Subcellular Localization of Divalent Metal Transporter 1 Isoforms
Open accessAbstract
Divalent metal transporter 1 (DMT1) is responsible for dietary-iron absorption from apical plasma membrane in the duodenum and iron acquisition from the transferrin cycle endosomes in peripheral tissues. Two isoforms of the DMT1 transcript generated by alternative splicing of the 3′ exons have been identified in mouse, rat, and human. These isoforms can be distinguished by the different C-terminal amino acid sequences and by the presence (DMT1A) or absence (DMT1B) of an iron response element located in the 3′ untranslated region of the mRNA. However, it has been still unknown whether the structural differences between the two DMT1 isoforms is functionally important. Here, we report that each DMT1 isoform exhibits a differential cell type–specific expression patterns and distinct subcellular localizations. DMT1A is predominantly expressed by epithelial cell lines, whereas DMT1B is expressed by the blood cell lines. In HEp-2 cells, GFP-tagged DMT1A is localized in late endosomes and lysosomes, whereas GFP-tagged DMT1B is localized in early endosomes. Using site-directed mutagenesis, a Y 555 XLXX sequence in the cytoplasmic tail of DMT1B has been identified as an important signal sequence for the early endosomal-targeting of DMT1B. In polarized MDCK cells, GFP-tagged DMT1A and DMT1B are localized in the apical plasma membrane and their respective specific endosomes. Disruption of the N-glycosylation sites in each of the DMT1 isoforms affects their polarized distribution into the apical plasma membrane but not their correct endosomal localization. Our data indicate that the cell type–specific expression patterns and the distinct subcellular localizations of two DMT1 isoforms may be involved in the different iron acquisition steps from the subcellular membranes in various cell types.
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“These mice also demonstrated an increase in markers of oxidative stress, including SOD activity, oxidative protein modifications, and apoptotic indicators (291).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [291]
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“Furthermore, generation of heterozygous ferritin H–null mutants shows brain iron levels similar to those of the wild type, despite a 50% expression of ferritin H that corresponded with increases in proteins involved in iron regulation, such as Tf, TfR, ferritin L, DMT1, and Cp (291).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [291]
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“Furthermore, generation of heterozygous ferritin H–null mutants shows brain iron levels similar to those of the wild type, despite a 50% expression of ferritin H that corresponded with increases in proteins involved in iron regulation, such as Tf, TfR, ferritin L, DMT1, and Cp (291).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [291]
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Metadata
- Authors
- Tabuchi, M., Tanaka, N., Nishida-Kitayama, J., Ohno, H., & Kishi, F.
- Affiliations
- Yamaguchi University (JP)
- Kanazawa University (JP)
- Center for Gene Research, Yamaguchi University, 1–1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan;
- Kagoshima University (JP)
- Venue
- Molecular Biology of the Cell
- Published
- 2002-12
- Volume
- 13
- Issue
- 12
- Pages
- 4371-4387
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC138640
- OpenAlex
- W2099892653
- Cited by
- 141
- References
- 52
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 9 · 2015: 8 · 2014: 3 · 2013: 3 · 2012: 7
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science Society
- Directorate for Biological Sciences
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- DMT1, alternative splicing, protein isoforms, subcellular localization, iron absorption, endosomal trafficking, early endosomes, late endosomes, lysosomes, apical membrane, cell polarity, N-glycosylation, cytoplasmic tail, iron-responsive element, cell type-specific gene expression
- MeSH terms
- Solute Carrier Family 11, Member 2, Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cytoplasm, Detergents, Dogs, Electrophoresis, Polyacrylamide Gel, Epithelial Cells, Exons, Genetic Complementation Test, Glycosylation, Humans, Iron, Microscopy, Fluorescence, Models, Biological, Molecular Sequence Data, Phenotype, Plasmids, Schizosaccharomyces, Subcellular Fractions, Transfection, Tumor Cells, Cultured, Immunoblotting, Blotting, Western, Mutagenesis, Site-Directed, Sequence Homology, Amino Acid, Alternative Splicing, Protein Structure, Tertiary, Biotinylation, Protein Isoforms, Membrane Microdomains, Cation Transport Proteins, Iron-Binding Proteins, Mice, Rats
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