ArticleThe Journal of biological chemistry2010
Lipid raft association and cholesterol sensitivity of P2X1-4 receptors for ATP: chimeras and point mutants identify intracellular amino-terminal residues involved in lipid regulation of P2X1 receptors.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Heat shock protein 90 inhibitors reduce trafficking of ATP-gated P2X1 receptors and human platelet responsiveness.The Journal of biological chemistry · 2012Trial
- Statins impair glucose uptake in tumor cells.Neoplasia (New York, N.Y.) · 2012Trial
- Review
- Structural basis for a central permeation pathway in the P2X1 receptor.Cell discovery · 2026Article
- Methodological guidelines for P2X receptor assays and data interpretation.Cell death & disease · 2026Review
- Cannabidiol (CBD) Induces Lipid Microdomain Disruption or Budding in Ternary Mixtures.The journal of physical chemistry. B · 2026Article
- Pannexin 3-mediated adenosine triphosphate release from pre-osteoblasts promotes osteoblast differentiation through P2X4 receptor activation.Frontiers in physiology · 2026Article
- Cryo-EM structures of the human P2X1 receptor reveal subtype-specific architecture and antagonism by supramolecular ligand-binding.Nature communications · 2024Article
- Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model.International journal of molecular sciences · 2024Article
- Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System.International journal of molecular sciences · 2022Review
- Extracellular Vesicles from Human Teeth Stem Cells Trigger ATP Release and Promote Migration of Human Microglia through P2X4 Receptor/MFG-E8-Dependent Mechanisms.International journal of molecular sciences · 2021Article
- Regulation of P2X1 receptors by modulators of the cAMP effectors PKA and EPAC.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Lipid rafts in glial cells: role in neuroinflammation and pain processing.Journal of lipid research · 2020Review
- Purinergic Signaling in Controlling Macrophage and T Cell Functions During Atherosclerosis Development.Frontiers in immunology · 2020Review
- Oxidized cholesterol species as signaling molecules in the brain: diabetes and Alzheimer's disease.Neuronal signaling · 2019Review
- CaThe Journal of biological chemistry · 2019Article
- Organization of ATP-gated P2X1 receptor intracellular termini in apo and desensitized states.The Journal of general physiology · 2019Article
- [Progress in the applications of high-speed atomic force microscopy in cell biology].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Review
- Modulation of DEG/ENaCs by Amphiphiles Suggests Sensitivity to Membrane Alterations.Biophysical journal · 2018Article
- P2X4 Receptor Function in the Nervous System and Current Breakthroughs in Pharmacology.Frontiers in pharmacology · 2017Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cholesterol-rich lipid rafts act as signaling microdomains and can regulate receptor function. We have shown in HEK293 cells recombinant P2X1-4 receptors (ATP-gated ion channels) are expressed in lipid rafts. Localization to flotillin-rich lipid rafts was reduced by the detergent Triton X-100. This sensitivity to Triton X-100 was concentration- and subunit-dependent, demonstrating differential association of P2X1-4 receptors with lipid rafts. The importance of raft association to ATP-evoked P2X receptor responses was determined in patch clamp studies. The cholesterol-depleting agents methyl-β-cyclodextrin or filipin disrupt lipid rafts and reduced P2X1 receptor currents by >90%. In contrast, ATP-evoked P2X2-4 receptor currents were unaffected by lipid raft disruption. To determine the molecular basis of cholesterol sensitivity, we generated chimeric receptors replacing portions of the cholesterol-sensitive P2X1 receptor with the corresponding region from the insensitive P2X2 receptor. These chimeras identified the importance of the intracellular amino-terminal region between the conserved protein kinase C site and the first transmembrane segment for the sensitivity to cholesterol depletion. Mutation of any of the variant residues between P2X1 and P2X2 receptors in this region in the P2X1 receptor (residues 20-23 and 27-29) to cysteine removed cholesterol sensitivity. Cholesterol depletion did not change the ATP sensitivity or cell surface expression of P2X1 receptors. This suggests that cholesterol is normally needed to facilitate the opening/gating of ATP-bound P2X1 receptor channels, and mutations in the pre-first transmembrane segment region remove this requirement.
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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.