ArticleThe Journal of cell biology2025
Sorting nexin 10 regulates lysosomal ionic homeostasis via ClC-7 by controlling PI(3,5)P2.
Article in The Journal of cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Spatiotemporal and quantitative analyses of phosphoinositides - fluorescent probe-and mass spectrometry-based approaches.FEBS letters · 2026Review
- The molecular and functional interplay between the osteopetrosis-associated proteins SNX10, OSTM1, and CLC-7 during mouse osteoclastogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Endosome maturation is orchestrated by inside-out proton signaling through a NaNature communications · 2026Article
- Endosome maturation is orchestrated by inside-out proton signaling through a NaResearch square · 2026Article
- LRRK2 integrates Rab and GABARAP interactions to sense and respond to distinct lysosomal stresses.bioRxiv : the preprint server for biology · 2025Article
- Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7.bioRxiv : the preprint server for biology · 2025Article
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- An advanced toolset to manipulate and monitor subcellular phosphatidylinositol 3,5-bisphosphate.The Journal of cell biology · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
Mutations or ablation of Snx10 are associated with neurodegeneration, blindness, and osteopetrosis. The similarities between osteoclasts and macrophages prompted us to analyze the role of Snx10 in phagocytosis. Deletion of Snx10 impaired phagosome resolution. Defective resolution was caused by reduced Cl- accumulation within (phago)lysosomes, replicating the phenotype reported in macrophages lacking ClC-7, a lysosomal 2Cl-/H+ antiporter. Delivery of ClC-7 to (phago)lysosomes was unaffected by ablation of Snx10, but its activity was markedly depressed. Snx10 was found to regulate ClC-7 activity indirectly by controlling the availability of phosphatidylinositol 3,5-bisphosphate (PI[3,5]P2), which inhibits ClC-7. By limiting the formation of PI(3,5)P2, Snx10 enables the accumulation of luminal Cl- in phagosomes and lysosomes, which is required for their optimal degradative function. Our data suggest that Snx10 regulates the delivery of PI 3-phosphate (PI[3]P), the precursor of PI(3,5)P2, from earlier endocytic compartments to (phago)lysosomes. By controlling the traffic of phosphoinositides, Snx10 regulates phagosomal resolution and possibly accounts for the impaired bone resorption in Snx10-deficient osteoclasts.
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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 Socratic graph.