ArticleProceedings of the National Academy of Sciences of the United States of America2012
Mechanism of proton/substrate coupling in the heptahelical lysosomal transporter cystinosin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- pH-mediated activation of the lysosomal arginine sensor SLC38A9.FEBS letters · 2026Article
- Cystinosin/Ers1 functions in redox homeostasis in the early secretory pathway.bioRxiv : the preprint server for biology · 2026Article
- pH-dependent regulation in SLC38A9.bioRxiv : the preprint server for biology · 2025Article
- Computational prediction of deleterious nonsynonymous SNPs in the CTNS gene: implications for cystinosis.BMC genomic data · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes.Nature cell biology · 2024Article
- Disulfidptosis decoded: a journey through cell death mysteries, regulatory networks, disease paradigms and future directions.Biomarker research · 2024Review
- Article
- Studies with Human-Induced Pluripotent Stem Cells Reveal That CTNS Mutations Can Alter Renal Proximal Tubule Differentiation.International journal of molecular sciences · 2023Article
- HemibiotrophicPlants (Basel, Switzerland) · 2023Article
- Article
- Structural basis for proton coupled cystine transport by cystinosin.Nature communications · 2022Article
- Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters.Cells · 2022Review
- Genetic Landscape of Nephropathic Cystinosis in Russian Children.Frontiers in genetics · 2022Article
- Arginine-selective modulation of the lysosomal transporter PQLC2 through a gate-tuning mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A selective transmembrane recognition mechanism by a membrane-anchored ubiquitin ligase adaptor.The Journal of cell biology · 2021Article
- The mechanism and regulation of vesicular glutamate transport: Coordination with the synaptic vesicle cycle.Biochimica et biophysica acta. Biomembranes · 2020Review
- A PQ-loop protein Ypq2 is involved in the exchange of arginine and histidine across the vacuolar membrane of Saccharomyces cerevisiae.Scientific reports · 2019Article
- A Genetic Screen for Investigating the Human Lysosomal CystineTransporter, Cystinosin.Scientific reports · 2018Article
- The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives.Nature reviews. Nephrology · 2017Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
Secondary active transporters use electrochemical gradients provided by primary ion pumps to translocate metabolites or drugs "uphill" across membranes. Here we report the ion-coupling mechanism of cystinosin, an unusual eukaryotic, proton-driven transporter distantly related to the proton pump bacteriorhodopsin. In humans, cystinosin exports the proteolysis-derived dimeric amino acid cystine from lysosomes and is impaired in cystinosis. Using voltage-dependence analysis of steady-state and transient currents elicited by cystine and neutralization-scanning mutagenesis of conserved protonatable residues, we show that cystine binding is coupled to protonation of a clinically relevant aspartate buried in the membrane. Deuterium isotope substitution experiments are consistent with an access of this aspartate from the lysosomal lumen through a deep proton channel. This aspartate lies in one of the two PQ-loop motifs shared by cystinosin with a set of eukaryotic membrane proteins of unknown function and is conserved in about half of them, thus suggesting that other PQ-loop proteins may translocate protons.
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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.