ArticleThe Journal of biological chemistry2019
Proximal tubule transferrin uptake is modulated by cellular iron and mediated by apical membrane megalin-cubilin complex and transferrin receptor 1.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- Azilsartan as a novel anti-ferriptotic agent via the upregulation of the Nrf2/HO-1/SLC7A11/GPX4 axis and downregulation of inflammatory pathways in folic acid-induced acute kidney injury in male mice.Toxicology reports · 2026Article
- Review
- Protein corona proteomics characterizes low-abundance plasma protein signatures and highlights ferroptosis-associated signals in uremic hemodialysis patients.Clinical proteomics · 2026Article
- Iron metabolism and ferroptosis: druggable targets to delay the progression of lupus nephritis.American journal of physiology. Renal physiology · 2026Review
- Iron Overload Accelerates Aging-Associated Kidney Injury in Mice: Implications for Iron Supplementation in the Elderly.Nutrients · 2025Article
- Transferrin receptors.Experimental & molecular medicine · 2025Review
- Iron-Deficiency Anemia Elevates Risk of Diabetic Kidney Disease in Type 2 Diabetes Mellitus.Journal of diabetes · 2025Article
- Antioxidative Function of Zinc and Its Protection Against the Onset and Progression of Kidney Disease Due to Cadmium.Biomolecules · 2025Review
- Crosstalk between ferroptosis and innate immune in diabetic kidney disease: mechanisms and therapeutic implications.Frontiers in immunology · 2025Review
- Machine learning and 4D-LFQ quantitative proteomic analysis explore the molecular mechanism of kidney stone formation.Heliyon · 2024Article
- Advance in Iron Metabolism, Oxidative Stress and Cellular Dysfunction in Experimental and Human Kidney Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Functional consequence of Iron dyshomeostasis and ferroptosis in systemic lupus erythematosus and lupus nephritis.Clinical immunology (Orlando, Fla.) · 2024Review
- Integrating tumor and healthy epithelium in a micro-physiology multi-compartment approach to study renal cell carcinoma pathophysiology.Scientific reports · 2024Article
- Iron metabolism and chronic inflammation in IgA nephropathy.Renal failure · 2023Review
- Receptor-associated protein impairs ligand binding to megalin and megalin-dependent endocytic flux in proximal tubule cells.American journal of physiology. Renal physiology · 2023Article
- Induction of Hepcidin Expression in the Renal Cortex of Sickle Cell Disease Mice.International journal of molecular sciences · 2023Article
- Estimation of health risks associated with dietary cadmium exposure.Archives of toxicology · 2023Review
- Ferroptosis: an important player in the inflammatory response in diabetic nephropathy.Frontiers in immunology · 2023Review
- Emerging roles of proximal tubular endocytosis in renal fibrosis.Frontiers in cell and developmental biology · 2023Review
- Angiotensin II type-1 receptor-associated protein interacts with transferrin receptor-1 and promotes its internalization.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Receptor-mediated endocytosis is responsible for reabsorption of transferrin (Tf) in renal proximal tubules (PTs). Although the role of the megalin-cubilin receptor complex (MCRC) in this process is unequivocal, modalities independent of this complex are evident but as yet undefined. Here, using immunostaining and Tf-flux assays, FACS analysis, and fluorescence imaging, we report localization of Tf receptor 1 (TfR1), the cognate Tf receptor mediating cellular holo-Tf (hTf) acquisition, to the apical brush border of the PT, with expression gradually declining along the PT in mouse and rat kidneys. In functional studies, hTf uptake across the apical membrane of cultured PT epithelial cell (PTEC) monolayers increased in response to decreased cellular iron after desferrioxamine (DFO) treatment. We also found that apical hTf uptake under basal conditions is receptor-associated protein (RAP)-sensitive and therefore mediated by the MCRC but becomes RAP-insensitive under DFO treatment, with concomitantly decreased megalin and cubilin expression levels and increased TfR1 expression. Thus, as well as the MCRC, TfR1 mediates hTf uptake across the PT apical brush border, but in conditions of decreased cellular iron, hTf uptake is predominated by augmented apical TfR1. In conclusion, both the MCRC and TfR1 mediate hTf uptake across apical brush border membranes of PTECs and reciprocally respond to decreased cellular iron. Our findings have implications for renal health, whole-body iron homeostasis, and pathologies arising from disrupted iron balance.
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