ArticleMolecular biology of the cell2002
Alternative splicing regulates the subcellular localization of divalent metal transporter 1 isoforms.
Article in Molecular biology of the cell, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 139 citations in OpenAlex.
- Disruption of iron metabolism resulting from Dmt1/Slc11a2 deficiency compromises Notch protein degradation and transcriptional activation.The FEBS journal · 2026Article
- Acidosis, Iron Dyshomeostasis and Inflammatory Injury.International journal of molecular sciences · 2026Review
- Acute endothelial stresses identify microRNA let-7b-5p and non-coding SLC11A2 (NRAMP2/DMT1) exon as biomarkers that overlap with those detected in malignant and non-malignant diseases.QJM : monthly journal of the Association of Physicians · 2025Article
- The solute carrier family 11 transporters: a bridge between iron homeostasis and tumor biology.Cell communication and signaling : CCS · 2025Review
- The Roles of DMT1 in Inflammatory and Degenerative Diseases.Molecular neurobiology · 2025Review
- Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cells.Frontiers in molecular biosciences · 2025Article
- Iron Metabolism and Inflammatory Mediators in Patients with Renal Dysfunction.International journal of molecular sciences · 2024Review
- The Endolysosomal Transporter DMT1 is Required for Morphine Regulation of Neuronal Ferritin Heavy Chain.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Internalization and Decrease of Duodenal DMT1 Involved in Transient Suppression of Iron Uptake in Short-Acting Mucosal Block.Biological trace element research · 2022Article
- Adaptive Changes Allow Targeting of Ferroptosis for Glioma Treatment.Cellular and molecular neurobiology · 2022Review
- Iron homeostasis and organismal aging.Ageing research reviews · 2021Review
- Article
- Molecular Mechanism of Nramp-Family Transition Metal Transport.Journal of molecular biology · 2021Review
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
- DMT1 Expression and Iron Levels at the Crossroads Between Aging and Neurodegeneration.Frontiers in neuroscience · 2019Review
- Targeted LC-MS/MS Proteomics-Based Strategy To Characterize in Vitro Models Used in Drug Metabolism and Transport Studies.Analytical chemistry · 2018Article
- Duplication and Sub/Neofunctionalization ofG3 (Bethesda, Md.) · 2017Article
- The iron chaperone poly(rC)-binding protein 2 forms a metabolon with the heme oxygenase 1/cytochrome P450 reductase complex for heme catabolism and iron transfer.The Journal of biological chemistry · 2017Article
- Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).Frontiers in genetics · 2017Article
- Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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