ArticleScientific reports2018
Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
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- Efficient and selective kidney targeting by chemically modified carbohydrate conjugates.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Imerslund-Gräsbeck syndrome in a child with a novel compound heterozygous mutations in the AMN gene: a case report.Italian journal of pediatrics · 2024Article
- Controversy between biopsy and risk in children with proteinuria: is there a paradigm war?BMC nephrology · 2024Article
- Identification and characterization of intact glycopeptides in human urine.Scientific reports · 2024Article
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- A novel SLC5A2 heterozygous variant in a family with familial renal glucosuria.Human genome variation · 2022Article
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- Novel pathogenic variants in CUBN uncouple proteinuria from renal function.Journal of translational medicine · 2022Article
- Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications.Physiological reviews · 2022Review
- Aging and its treatment with vitamin C: a comprehensive mechanistic review.Molecular biology reports · 2021Review
- Changes in the Expression of Renal Brush Border MembraneBiomolecules · 2021Article
- A vector whitefly endocytic receptor facilitates the entry of begomoviruses into its midgut cells via binding to virion capsid proteins.PLoS pathogens · 2020Article
- Proteinuria as a presenting sign of combined methylmalonic acidemia and homocysteinemia: case report.BMC medical genetics · 2020Article
- Variants inAmerican journal of cancer research · 2020Article
- Article
- Loss of Cubilin, the intrinsic factor-vitamin B12 receptor, impairs visceral endoderm endocytosis and endodermal patterning in the mouse.Scientific reports · 2019Article
- Structural assembly of the megadalton-sized receptor for intestinal vitamin BNature communications · 2018Article
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Authors and funding
14 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria. Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless. We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients. A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin. The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS. Notably, the interaction between cubilin and amnionless was not sufficient, but amnionless-mediated glycosylation of cubilin was necessary for their surface expression. Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting. These results delineated the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells.
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