ArticleNature communications2024
Cilia-enriched oxysterol 7β,27-DHC is required for polycystin ion channel activation.
Article in Nature communications, 2024. 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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Who cites it
14 citing papers in PubMed.
- Ciliary Membrane Lipid Homeostasis in Health and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- Cilia-to-basement membrane signaling is a biomechanical driver in models of autosomal dominant polycystic kidney disease.The Journal of clinical investigation · 2026Article
- Structural basis of lipid-dependent allosteric gating mechanisms for PC1-PC2 ion channel.Nature communications · 2026Article
- The Important Role of Polycystin in the Skeletal System.Calcified tissue international · 2026Review
- Pathophysiological significance of cholesterol in ciliopathies.Fujita medical journal · 2026Article
- Lipid ciliology: specialized ciliary membrane lipids in physiology and disease.Frontiers in cell and developmental biology · 2026Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Ion channel function of polycystin-2/polycystin-1 heteromer revealed by structure-guided mutagenesis.FEBS letters · 2025Article
- Cholesterol ensures ciliary polycystin-2 localization to prevent polycystic kidney disease.Life science alliance · 2025Article
- Hyperosmolality activates polycystin-2 and TRPM4 in renal primary cilium.Pflugers Archiv : European journal of physiology · 2025Article
- The Influence of Phosphoinositide Lipids in the Molecular Biology of Membrane Proteins: Recent Insights from Simulations.Journal of molecular biology · 2025Review
- Emerging mechanistic understanding of cilia function in cellular signalling.Nature reviews. Molecular cell biology · 2024Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Polycystin-1 (PC-1) and PC-2 form a heteromeric ion channel complex that is abundantly expressed in primary cilia of renal epithelial cells. This complex functions as a non-selective cation channel, and mutations within the polycystin complex cause autosomal dominant polycystic kidney disease (ADPKD). The spatial and temporal regulation of the polycystin complex within the ciliary membrane remains poorly understood. Using both whole-cell and ciliary patch-clamp recordings, we identify a cilia-enriched oxysterol, 7β,27-dihydroxycholesterol (DHC), that serves as a necessary activator of the polycystin complex. We further identify an oxysterol-binding pocket within PC-2 and showed that mutations within this binding pocket disrupt 7β,27-DHC-dependent polycystin activation. Pharmacologic and genetic inhibition of oxysterol synthesis reduces channel activity in primary cilia. In summary, our findings reveal a regulator of the polycystin complex. This oxysterol-binding pocket in PC-2 may provide a specific target for potential ADPKD therapeutics.
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