ArticleProceedings of the National Academy of Sciences of the United States of America1996
Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Receptor-mediated endocytosis by Megalin: Exploring its role in ligand interaction and disease mechanisms.Genes & diseases · 2026Review
- Integrative structural analysis of the human LRP2-LRPAP1 complex reveals multiple regulatory sites.Communications biology · 2026Article
- Inherited disorders of cobalamin metabolism in childhood: biochemical and clinical perspectives.Frontiers in nutrition · 2026Review
- CD320 Receptor and Vitamin B12 as Potential Targets for Anti-Cancer Therapy.International journal of molecular sciences · 2025Review
- Maternal Vitamin B12 in Pregnancy and Placental Development.Journal of nutrition and metabolism · 2024Review
- Dietary supplementation of cystinotic mice by lysine inhibits the megalin pathway and decreases kidney cystine content.Scientific reports · 2023Article
- Receptor-associated protein impairs ligand binding to megalin and megalin-dependent endocytic flux in proximal tubule cells.American journal of physiology. Renal physiology · 2023Article
- Identification of Potential Megalin/Cubilin Substrates Using Extensive Proteomics Quantification from Kidney Megalin-Knockdown Mice.The AAPS journal · 2022Article
- Megalin and Vitamin D Metabolism-Implications in Non-Renal Tissues and Kidney Disease.Nutrients · 2022Review
- Newly Identified Deficiencies in the Multiple Sclerosis Central Nervous System and Their Impact on the Remyelination Failure.Biomedicines · 2022Review
- Review of cobalamin status and disorders of cobalamin metabolism in dogs.Journal of veterinary internal medicine · 2020Review
- Kinetic analysis of transcellular passage of the cobalamin-transcobalamin complex in Caco-2 monolayers.Molecular biology of the cell · 2019Article
- Mice lacking the transcobalamin-vitamin B12 receptor, CD320, suffer from anemia and reproductive deficits when fed vitamin B12-deficient diet.Human molecular genetics · 2018Article
- LRP2 gene variants and their haplotypes strongly influence the risk of developing neural tube defects in the fetus: a family-triad study from South India.Metabolic brain disease · 2018Article
- Tissue distribution of oral vitamin B12 is influenced by B12 status and B12 form: an experimental study in rats.European journal of nutrition · 2018Article
- Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.Journal of the American Society of Nephrology : JASN · 2018Article
- Conserved and Divergent Molecular and Anatomic Features of Human and Mouse Nephron Patterning.Journal of the American Society of Nephrology : JASN · 2018Article
- Multifunctional nanoparticles for real-time evaluation of toxicity during fetal development.PloS one · 2018Article
- A missense mutation inOncotarget · 2017Article
- Maternofetal transport of vitamin BFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
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8 authors.
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Abstract
Kidney cortex is a main target for circulating vitamin B12 (cobalamin) in complex with transcobalamin (TC). Ligand blotting of rabbit kidney cortex with rabbit 125I-TC-B12 and human TC-57Co-B12 revealed an exclusive binding to megalin, a 600-kDa endocytic receptor present in renal proximal tubule epithelium and other absorptive epithelia. The binding was Ca2+ dependent and inhibited by receptor-associated protein (RAP). Surface plasmon resonance analysis demonstrated a high-affinity interaction between purified rabbit megalin and rabbit TC-B12 but no measurable affinity of the vitamin complex for the homologous alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor related protein (LRP). 125I-TC-B12 was efficiently endocytosed in a RAP-inhibitable manner in megalin-expressing rat yolk sac carcinoma cells and in vivo microperfused rat proximal tubules. The radioactivity in the tubules localized to the endocytic compartments and a similar apical distribution in the proximal tubules was demonstrated after intravenous injection of 125I-TC-B12. The TC-B12 binding sites in the proximal tubule epithelium colocalized with megalin as shown by ligand binding to cryosections of rat kidney cortex, and the binding was inhibited by anti-megalin polyclonal antibody, EDTA, and RAP. These data show a novel nutritional dimension of megalin as a receptor involved in the cellular uptake of vitamin B12. The expression of megalin in absorptive epithelia in the kidney and other tissues including yolk sac and placenta suggests a role of the receptor in vitamin B12 homeostasis and fetal vitamin B12 supply.
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