ArticleCurrent biology : CB2023
A BORC-dependent molecular pathway for vesiculation of cell corpse phagolysosomes.
Article in Current biology : CB, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 25 citations in OpenAlex.
- BORC assemblies integrate BLOC-1 subunits to diversify endosomal trafficking functions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The transcription factor SKN-1 drives lysosomal enlargement during aging to maintain function.PLoS biology · 2025Article
- Kinesins inOpen biology · 2025Review
- CED-3 caspase promotes dismantling but not onset of non-apoptotic linker cell death inbioRxiv : the preprint server for biology · 2025Article
- High-throughput behavioural phenotyping of 25 C. elegans disease models including patient-specific mutations.BMC biology · 2025Article
- BLOC-1 and BORC: Complex regulators of endolysosomal dynamics.Cell chemical biology · 2025Review
- Expression of miRNA-338-3p/miRNA-1250-5p/miRNA-3065-5p clusters in peripheral blood mononuclear cells of ischemic stroke.Scientific reports · 2025Article
- Evolutionary origins of the lysosome-related organelle sorting machinery reveal ancient homology in post-endosome trafficking pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss.Journal of cell science · 2024Article
- VAMP5 promotes Fcγ receptor-mediated phagocytosis and regulates phagosome maturation in macrophages.Molecular biology of the cell · 2024Article
- Two-pore channels regulate endomembrane tension to enable remodeling and resolution of phagolysosomes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A genome-wide CRISPR functional survey of the human phagocytosis molecular machinery.Life science alliance · 2023Article
- Large vesicle extrusions fromeLife · 2023Article
- Phagocytosis: Phagolysosome vesiculation promotes cell corpse degradation.Current biology : CB · 2023Article
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5 authors at 3 institutions in 2 countries.
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Abstract
Phagocytic clearance is important to provide cells with metabolites and regulate immune responses, but little is known about how phagolysosomes finally resolve their phagocytic cargo of cell corpses, cell debris, and pathogens. While studying the phagocytic clearance of non-apoptotic polar bodies in C. elegans, we previously discovered that phagolysosomes tubulate into small vesicles to facilitate corpse clearance within 1.5 h. Here, we show that phagolysosome vesiculation depends on amino acid export by the solute transporter SLC-36.1 and the activation of TORC1. We demonstrate that downstream of TORC1, BLOC-1-related complex (BORC) is de-repressed by Ragulator through the BORC subunit BLOS-7. In addition, the BORC subunit SAM-4 is needed continuously to recruit the small GTPase ARL-8 to the phagolysosome for tubulation. We find that disrupting the regulated GTP-GDP cycle of ARL-8 reduces tubulation by kinesin-1, delays corpse clearance, and mislocalizes ARL-8 away from lysosomes. We also demonstrate that mammalian phagocytes use BORC to promote phagolysosomal degradation, confirming the conserved importance of TOR and BORC. Finally, we show that HOPS is required after tubulation for the rapid degradation of cargo in small phagolysosomal vesicles, suggesting that additional rounds of lysosome fusion occur. Thus, by observing single phagolysosomes over time, we identified the molecular pathway regulating phagolysosome vesiculation that promotes efficient resolution of phagocytosed cargos.
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