ArticleThe Journal of cell biology2020
PQLC2 recruits the C9orf72 complex to lysosomes in response to cationic amino acid starvation.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- The C9orf72/SMCR8 complex maintains microglial homeostasis via RAB8A-ESCRT-mediated lysosomal repair.The EMBO journal · 2026Article
- Vacuole pH loss triggers ESCRT-dependent plasma membrane remodeling to prevent amino acid toxicity.bioRxiv : the preprint server for biology · 2026Article
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- Longitudinal plasma proteomics: relation to incident Alzheimer's disease dementia and biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Eukaryote-Wide Distribution of a Family of Longin Domain-Containing GAP Complexes for Small GTPases.Traffic (Copenhagen, Denmark) · 2025Article
- JIP4 deficiency causes a lysosomal storage disease arising from impaired cystine efflux.bioRxiv : the preprint server for biology · 2025Article
- Lysosomal TMEM165 controls cellular ion homeostasis and survival by mediating lysosomal CaNature communications · 2025Article
- A STING-CASM-GABARAP pathway activates LRRK2 at lysosomes.The Journal of cell biology · 2025Article
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition.The EMBO journal · 2024Article
- MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes.Nature cell biology · 2024Article
- Lysosomal TBK1 Responds to Amino Acid Availability to Relieve Rab7-Dependent mTORC1 Inhibition.bioRxiv : the preprint server for biology · 2023Article
- Mitochondrial Dysfunction in Repeat Expansion Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Article
- C9ORF72 suppresses JAK-STAT mediated inflammation.iScience · 2023Article
- Longin domain GAP complexes in nutrient signalling, membrane traffic and neurodegeneration.FEBS letters · 2023Review
- Autophagy and neurodegeneration: Unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology.Frontiers in cellular neuroscience · 2023Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The C9orf72 protein is required for normal lysosome function. In support of such functions, C9orf72 forms a heterotrimeric complex with SMCR8 and WDR41 that is recruited to lysosomes when amino acids are scarce. These properties raise questions about the identity of the lysosomal binding partner of the C9orf72 complex and the amino acid-sensing mechanism that regulates C9orf72 complex abundance on lysosomes. We now demonstrate that an interaction with the lysosomal cationic amino acid transporter PQLC2 mediates C9orf72 complex recruitment to lysosomes. This is achieved through an interaction between PQLC2 and WDR41. The interaction between PQLC2 and the C9orf72 complex is negatively regulated by arginine, lysine, and histidine, the amino acids that PQLC2 transports across the membrane of lysosomes. These results define a new role for PQLC2 in the regulated recruitment of the C9orf72 complex to lysosomes and reveal a novel mechanism that allows cells to sense and respond to changes in the availability of cationic amino acids within lysosomes.
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Registered trials
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.