ArticleProceedings of the National Academy of Sciences of the United States of America2012
Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy.
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. An erratum has been issued. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 178 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Clinical practice recommendations for the diagnosis and management of nephropathic cystinosis.Nature reviews. Nephrology · 2026Review
- Vsb1, Ypq1, and Ypq2 control dynamic cationic amino acid storage in the yeast vacuole.Life science alliance · 2026Article
- pH-mediated activation of the lysosomal arginine sensor SLC38A9.FEBS letters · 2026Article
- Lysosome-derived methylated arginine is a signalling metabolite controlling the lipidome.Nature cell biology · 2026Article
- Molecular Basis of Rare Inherited Tubulopathies of the Kidney: A Primer for Clinicians.International journal of molecular sciences · 2026Review
- Cystinosin/Ers1 functions in redox homeostasis in the early secretory pathway.bioRxiv : the preprint server for biology · 2026Article
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- Inhibition of Low-Density Lipoprotein Oxidation by Cysteamine, Cystamine, Cysteine and Cystine at Lysosomal pH and pH 7.4.Antioxidants (Basel, Switzerland) · 2025Article
- pH-dependent regulation in SLC38A9.bioRxiv : the preprint server for biology · 2025Article
- Lysosomal reduced thiols are essential for mouse embryonic development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lysosomal quality control Review.Autophagy · 2025Review
- JIP4 deficiency causes a lysosomal storage disease arising from impaired cystine efflux.bioRxiv : the preprint server for biology · 2025Article
- BiDAC-dependent degradation of plasma membrane proteins by the endolysosomal system.Nature communications · 2025Article
- Any1 is a phospholipid scramblase involved in endosome biogenesis.The Journal of cell biology · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Targeting oxidative stress-induced lipid peroxidation enhances podocyte function in cystinosis.Journal of translational medicine · 2025Article
- Protocol for purifying and reconstituting a vacuole membrane transporter Ypq1 into proteoliposomes.STAR protocols · 2024Article
- Article
- MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes.Nature cell biology · 2024Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystinosin, the lysosomal cystine exporter defective in cystinosis, is the founding member of a family of heptahelical membrane proteins related to bacteriorhodopsin and characterized by a duplicated motif termed the PQ loop. PQ-loop proteins are more frequent in eukaryotes than in prokaryotes; except for cystinosin, their molecular function remains elusive. In this study, we report that three yeast PQ-loop proteins of unknown function, Ypq1, Ypq2, and Ypq3, localize to the vacuolar membrane and are involved in homeostasis of cationic amino acids (CAAs). We also show that PQLC2, a mammalian PQ-loop protein closely related to yeast Ypq proteins, localizes to lysosomes and catalyzes a robust, electrogenic transport that is selective for CAAs and strongly activated at low extracytosolic pH. Heterologous expression of PQLC2 at the yeast vacuole rescues the resistance phenotype of an ypq2 mutant to canavanine, a toxic analog of arginine efficiently transported by PQLC2. Finally, PQLC2 transports a lysine-like mixed disulfide that serves as a chemical intermediate in cysteamine therapy of cystinosis, and PQLC2 gene silencing trapped this intermediate in cystinotic cells. We conclude that PQLC2 and Ypq1-3 proteins are lysosomal/vacuolar exporters of CAAs and suggest that small-molecule transport is a conserved feature of the PQ-loop protein family, in agreement with its distant similarity to SWEET sugar transporters and to the mitochondrial pyruvate carrier. The elucidation of PQLC2 function may help improve cysteamine therapy. It may also clarify the origin of CAA abnormalities in Batten disease.
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