ArticleJournal of the American Society of Nephrology : JASN2016
Cystinosin is a Component of the Vacuolar H+-ATPase-Ragulator-Rag Complex Controlling Mammalian Target of Rapamycin Complex 1 Signaling.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- Clinical practice recommendations for the diagnosis and management of nephropathic cystinosis.Nature reviews. Nephrology · 2026Review
- Review
- Cystinosin regulates NaEMBO reports · 2026Article
- Cystinosin/Ers1 functions in redox homeostasis in the early secretory pathway.bioRxiv : the preprint server for biology · 2026Article
- Advances in Pharmacological Treatments for Cystinosis: Cysteamine and Its Alternatives.ACS pharmacology & translational science · 2026Review
- Cystinosis and Cellular Energy Failure: Mitochondria at the Crossroads.International journal of molecular sciences · 2026Review
- From Molecular Understanding and Pathophysiology to Disease Management; A Practical Approach and Guidance to the Management of the Ocular Manifestations of Cystinosis.International journal of molecular sciences · 2025Review
- Hypothesis: Taurine therapy of nephropathic cystinosis may correct the deficiencies of cysteamine therapy.Molecular genetics and metabolism reports · 2025Article
- Review: Utility of mass spectrometry in rare disease research and diagnosis.NPJ genomic medicine · 2025Review
- Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Cystinosin is involved in NabioRxiv : the preprint server for biology · 2025Article
- Ketogenic Diet and Progression of Kidney Disease in Animal Models of Nephropathic Cystinosis.Journal of the American Society of Nephrology : JASN · 2024Article
- Rag-Ragulator is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity.eLife · 2024Article
- Reconstitution of Rab11-FIP4 Expression Rescues Cellular Homeostasis in Cystinosis.Molecular and cellular biology · 2024Article
- Studies with Human-Induced Pluripotent Stem Cells Reveal That CTNS Mutations Can Alter Renal Proximal Tubule Differentiation.International journal of molecular sciences · 2023Article
- Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems, Part II: Long-Term Stability and Clinical Ocular Biopermanence.Pharmaceutics · 2023Article
- Dietary supplementation of cystinotic mice by lysine inhibits the megalin pathway and decreases kidney cystine content.Scientific reports · 2023Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystinosis is a rare autosomal recessive storage disorder characterized by defective lysosomal efflux of cystine due to mutations in the CTNS gene encoding the lysosomal cystine transporter, cystinosin. Lysosomal cystine accumulation leads to crystal formation and functional impairment of multiple organs. Moreover, cystinosis is the most common inherited cause of renal Fanconi syndrome in children. Oral cysteamine therapy delays disease progression by reducing intracellular cystine levels. However, because cysteamine does not correct all complications of cystinosis, including Fanconi syndrome, we hypothesized that cystinosin could have novel roles in addition to transporting cystine out of the lysosome. By coimmunoprecipitation experiments and mass spectrometry, we found cystinosin interacts with almost all components of vacuolar H(+)-ATPase and the Ragulator complex and with the small GTPases Ras-related GTP-binding protein A (RagA) and RagC. Furthermore, the mammalian target of rapamycin complex 1 (mTORC1) pathway was downregulated in proximal tubular cell lines derived from Ctns(-/-) mice. Decrease of lysosomal cystine levels by cysteamine did not rescue mTORC1 activation in these cells, suggesting that the downregulation of mTORC1 is due to the absence of cystinosin rather than to the accumulation of cystine. Our results show a dual role for cystinosin as a cystine transporter and as a component of the mTORC1 pathway, and provide an explanation for the appearance of Fanconi syndrome in cystinosis. Furthermore, this study highlights the need to develop new treatments not dependent on lysosomal cystine depletion alone for this devastating disease.
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