ArticleProceedings of the National Academy of Sciences of the United States of America2016
Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-related plasma membrane protein rBAT/SLC3A1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 108 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Selenocystine-based fluorescence assay combined with structural prediction for functional analysis of cystine transporter variants in cystinuria.Journal of Zhejiang University. Science. B · 2026Article
- Possible role of ribosome biogenesis in the recovery from transient hepatic damage caused by ethylene glycol in rats.Forensic toxicology · 2026Article
- Zinc dynamics in the pluripotent stem cells during maintenance of pluripotency and pancreatic differentiation.Scientific reports · 2026Article
- Oncogenic role of the SLC7A13-SLC3A1 cystine transporter in human luminal breast cancer and its cryo-EM structure.Protein & cell · 2026Article
- Glutathione Synthesis via the Cystine/Glutamate Transporter Promotes the Formation of Tertiary Lymphoid Structures in the Kidney.Journal of the American Society of Nephrology : JASN · 2026Article
- Na/K-ATPase in the renal proximal tubule cell: classic & novel roles in sodium handling.Frontiers in physiology · 2026Review
- Structural insights into cationic amino acid transport and viral receptor engagement by CAT1.Nature communications · 2025Article
- Efficient kidney gene transfer and proximal tubule transduction using self-complementary AAV.cc47 vectors.Molecular therapy. Methods & clinical development · 2025Article
- A Cystine Transporter Mediates Nutrient Acquisition and Redox Balance During Wheat Stripe Rust Infection.Molecular plant pathology · 2025Article
- Genetic and clinical characteristics of Japanese cystinuria with exon and exon-intron boundary variants.Scientific reports · 2025Article
- Role of Transport Proteins for the Renal Handling of L-Arginine and Related Derivatives.International journal of molecular sciences · 2025Review
- The Role of Solute Carriers in the Metabolic Reprogramming of Skin Diseases.Clinical reviews in allergy & immunology · 2025Review
- ATF4 in proximal tubules modulates kidney function and modifies the metabolome.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Mitochondrial SLC3A1 regulates sexual dimorphism in cystinuria.Genes & diseases · 2025Article
- Differential uptake of arginine derivatives by the human heteromeric amino acid transporter bNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Rare pathogenic structural variants show potential to enhance prostate cancer germline testing for African men.Nature communications · 2025Article
- Convergent Evolution and Predictability of Gene Copy Numbers Associated with Diets in Mammals.Genome biology and evolution · 2025Article
- Mechanisms involved in aminoacidurias: impacts of genetic and environmental factors.Current research in physiology · 2025Review
- Serum lncRNAs TUG1, H19, and NEAT1 and their target miR-29b/SLC3A1 axis as possible biomarkers of preeclampsia: Potential clinical insights.Non-coding RNA research · 2024Article
6 more citing papers are in PubMed but not listed here.
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15 authors at 5 institutions in 2 countries.
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Abstract
Heterodimeric amino acid transporters play crucial roles in epithelial transport, as well as in cellular nutrition. Among them, the heterodimer of a membrane protein b(0,+)AT/SLC7A9 and its auxiliary subunit rBAT/SLC3A1 is responsible for cystine reabsorption in renal proximal tubules. The mutations in either subunit cause cystinuria, an inherited amino aciduria with impaired renal reabsorption of cystine and dibasic amino acids. However, an unsolved paradox is that rBAT is highly expressed in the S3 segment, the late proximal tubules, whereas b(0,+)AT expression is highest in the S1 segment, the early proximal tubules, so that the presence of an unknown partner of rBAT in the S3 segment has been proposed. In this study, by means of coimmunoprecipitation followed by mass spectrometry, we have found that a membrane protein AGT1/SLC7A13 is the second partner of rBAT. AGT1 is localized in the apical membrane of the S3 segment, where it forms a heterodimer with rBAT. Depletion of rBAT in mice eliminates the expression of AGT1 in the renal apical membrane. We have reconstituted the purified AGT1-rBAT heterodimer into proteoliposomes and showed that AGT1 transports cystine, aspartate, and glutamate. In the apical membrane of the S3 segment, AGT1 is suggested to locate itself in close proximity to sodium-dependent acidic amino acid transporter EAAC1 for efficient functional coupling. EAAC1 is proposed to take up aspartate and glutamate released into luminal fluid by AGT1 due to its countertransport so that preventing the urinary loss of aspartate and glutamate. Taken all together, AGT1 is the long-postulated second cystine transporter in the S3 segment of proximal tubules and a possible candidate to be involved in isolated cystinuria.
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