ArticleProceedings of the National Academy of Sciences of the United States of America2021
Arginine-selective modulation of the lysosomal transporter PQLC2 through a gate-tuning mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Lysosome-derived methylated arginine is a signalling metabolite controlling the lipidome.Nature cell biology · 2026Article
- 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
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- Lysosome as a Chemical Reactor.International journal of molecular sciences · 2025Review
- pH-dependent regulation in SLC38A9.bioRxiv : the preprint server for biology · 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
- Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lysosomal membrane transporter purification and reconstitution for functional studies.Molecular biology of the cell · 2024Article
- Lysosomes in retinal health and disease.Trends in neurosciences · 2023Review
- Article
- Organelle transporters and inter-organelle communication as drivers of metabolic regulation and cellular homeostasis.Molecular metabolism · 2022Review
- Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters.Cells · 2022Review
- Amino Acid Homeostasis in Mammalian Cells with a Focus on Amino Acid Transport.The Journal of nutrition · 2022Article
- Picking the arginine lock on PQLC2 cycling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomes degrade excess or damaged cellular components and recycle their building blocks through membrane transporters. They also act as nutrient-sensing signaling hubs to coordinate cell responses. The membrane protein PQ-loop repeat-containing protein 2 (PQLC2; "picklock two") is implicated in both functions, as it exports cationic amino acids from lysosomes and serves as a receptor and amino acid sensor to recruit the C9orf72/SMCR8/WDR41 complex to lysosomes upon nutrient starvation. Its transport activity is essential for drug treatment of the rare disease cystinosis. Here, we quantitatively studied PQLC2 transport activity using electrophysiological and biochemical methods. Charge/substrate ratio, intracellular pH, and reversal potential measurements showed that it operates in a uniporter mode. Thus, PQLC2 is uncoupled from the steep lysosomal proton gradient, unlike many lysosomal transporters, enabling bidirectional cationic amino acid transport across the organelle membrane. Surprisingly, the specific presence of arginine, but not other substrates (lysine, histidine), in the discharge ("
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