ArticlePloS one2012
Mannose 6-phosphate receptor and sortilin mediated endocytosis of α-galactosidase A in kidney endothelial cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Identification of Potential Proteins Interacting with α-Galactosidase A to Analyze the Pathogenesis of Fabry Disease.International journal of molecular sciences · 2026Article
- Comparative study on incorporation of three recombinant human α-galactosidase A drugs (agalsidases) into cultured fibroblasts and organs/tissues of Fabry mice.Molecular genetics and metabolism reports · 2024Article
- Does administration of hydroxychloroquine/amiodarone affect the efficacy of enzyme replacement therapy for Fabry mice?Molecular genetics and metabolism reports · 2024Article
- Preclinical evaluation of FLT190, a liver-directed AAV gene therapy for Fabry disease.Gene therapy · 2023Article
- A universal GlycoDesign for lysosomal replacement enzymes to improve circulation time and biodistribution.Frontiers in bioengineering and biotechnology · 2023Article
- Emerging roles of proximal tubular endocytosis in renal fibrosis.Frontiers in cell and developmental biology · 2023Review
- Gene Expression Analysis inInternational journal of molecular sciences · 2022Article
- Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience.PloS one · 2022Article
- Migalastat Tissue Distribution: Extrapolation From Mice to Humans Using Pharmacokinetic Modeling and Comparison With Agalsidase Beta Tissue Distribution in Mice.Clinical pharmacology in drug development · 2021Article
- Surface plasmon resonance analysis of complex formation of therapeutic recombinant lysosomal enzymes with domain 9 of human cation-independent mannose 6-phosphate receptor.Molecular genetics and metabolism reports · 2020Article
- Rapid Clathrin-Mediated Uptake of Recombinant α-Gal-A to Lysosome Activates Autophagy.Biomolecules · 2020Article
- The glycosylation design space for recombinant lysosomal replacement enzymes produced in CHO cells.Nature communications · 2019Article
- Quantitative Proteome Analysis of Mouse Liver Lysosomes Provides Evidence for Mannose 6-phosphate-independent Targeting Mechanisms of Acid Hydrolases in Mucolipidosis II.Molecular & cellular proteomics : MCP · 2017Article
- Association Between Progranulin and Gaucher Disease.EBioMedicine · 2016Article
- Molecular basis for globotriaosylceramide regulation and enzyme uptake in immortalized aortic endothelial cells from Fabry mice.Journal of inherited metabolic disease · 2016Article
- Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology.Neural regeneration research · 2016Review
- Mannose receptor-mediated delivery of moss-made α-galactosidase A efficiently corrects enzyme deficiency in Fabry mice.Journal of inherited metabolic disease · 2016Article
- A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells.Nature communications · 2015Article
- Sortilin and lipoprotein metabolism: making sense out of complexity.Current opinion in lipidology · 2014Review
- Receptor-associated protein blocks internalization and cytotoxicity of myeloma light chain in cultured human proximal tubular cells.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Prominent vasculopathy in Fabry disease patients is caused by excessive intracellular accumulation of globotriaosylceramide (GL-3) throughout the vascular endothelial cells causing progressive cerebrovascular, cardiac and renal impairments. The vascular lesions lead to myocardial ischemia, atherogenesis, stroke, aneurysm, thrombosis, and nephropathy. Hence, injury to the endothelial cells in the kidney is a key mechanism in human glomerular disease and endothelial cell repair is an important therapeutic target. We investigated the mechanism of uptake of α-galactosidase A (α-Gal A) in renal endothelial cells, in order to clarify if the recombinant enzyme is targeted to the lysosomes via the universal mannose 6-phosphate receptor (M6PR) and possibly other receptors. Immunohistochemical localization of infused recombinant α-Gal A in a renal biopsy from a classic Fabry disease patient showed that recombinant protein localize in the endothelial cells of the kidney. Affinity purification studies using α-Gal A resins identified M6PR and sortilin as α-Gal A receptors in cultured glomerular endothelial cells. Immunohistochemical analyses of normal human kidney with anti-sortilin and anti-M6PR showed that sortilin and M6PR were expressed in the endothelium of smaller and larger vessels. Uptake studies in cultured glomerular endothelial cells of α-Gal A labeled with fluorescence and (125)I showed by inhibition with RAP and M6P that sortilin and M6PR mediated uptake of α-Gal A. Biacore studies revealed that α-Gal A binds to human M6PR with very high affinity, but M6PR also binds to sortilin in a way that prevents α-Gal A binding to sortilin. Taken together, our data provide evidence that sortilin is a new α-Gal A receptor expressed in renal endothelial cells and that this receptor together with the M6PR is able to internalize circulating α-Gal A during enzyme replacement therapy in patients with Fabry disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.