ArticleThe Journal of biological chemistry2014
Plasma membrane cholesterol as a regulator of human and rodent P2X7 receptor activation and sensitization.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 77 citations in OpenAlex.
- Genetic Variations in the P2X7 Receptor: Opportunities and Challenges for Drug Development.International journal of molecular sciences · 2025Review
- A polycyclic scaffold identified by structure-based drug design effectively inhibits the human P2X7 receptor.Nature communications · 2025Article
- Structural basis of the multiple ligand binding mechanisms of the P2X1 receptor.Acta pharmacologica Sinica · 2025Article
- Ionotropic purinergic receptor 7 (P2X7) channel structure and pharmacology provides insight regarding non-nucleotide agonism.Channels (Austin, Tex.) · 2024Review
- Cryo-EM structures of the human P2X1 receptor reveal subtype-specific architecture and antagonism by supramolecular ligand-binding.Nature communications · 2024Article
- Deep learning structural insights into heterotrimeric alternatively spliced P2X7 receptors.Purinergic signalling · 2024Article
- Loss-of-function/gain-of-function polymorphisms of the ATP sensitive P2X7R influence sepsis, septic shock, pneumonia, and survival outcomes.Frontiers in immunology · 2024Article
- Research progress of SREBP and its role in the pathogenesis of autoimmune rheumatic diseases.Frontiers in immunology · 2024Review
- Role of Oxysterols in Ocular Degeneration Mechanisms and Involvement of P2X7 Receptor.Advances in experimental medicine and biology · 2024Article
- Untangling Macropore Formation and Current Facilitation in P2X7.International journal of molecular sciences · 2023Review
- Article
- Purinergic signaling: Diverse effects and therapeutic potential in cancer.Frontiers in oncology · 2023Review
- Article
- Alternatively Spliced Isoforms of the P2X7 Receptor: Structure, Function and Disease Associations.International journal of molecular sciences · 2022Review
- Hypercholesterolemia Negatively Regulates P2X7-Induced Cellular Function in CD4International journal of molecular sciences · 2022Article
- Using Symmetrical Organic Cation Solutions to Study P2X7 Ion Permeation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Using Whole-Cell Electrophysiology and Patch-Clamp Photometry to Characterize P2X7 Receptor Currents.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Methods for Studying Cholesterol-Dependent Regulation of P2X7 Receptors.Methods in molecular biology (Clifton, N.J.) · 2022Article
- To inhibit or to boost the ATP/P2RX7 pathway to fight cancer-that is the question.Purinergic signalling · 2021Review
- P2X4 Receptors Mediate CaInternational journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
P2X7 receptors are nonselective cation channels gated by high extracellular ATP, but with sustained activation, receptor sensitization occurs, whereby the intrinsic pore dilates, making the cell permeable to large organic cations, which eventually leads to cell death. P2X7 receptors associate with cholesterol-rich lipid rafts, but it is unclear how this affects the properties of the receptor channel. Here we show that pore-forming properties of human and rodent P2X7 receptors are sensitive to perturbations of cholesterol levels. Acute depletion of cholesterol with 5 mm methyl-β-cyclodextrin (MCD) caused a substantial increase in the rate of agonist-evoked pore formation, as measured by the uptake of ethidium dye, whereas cholesterol loading inhibited this process. Patch clamp analysis of P2X7 receptor currents carried by Na(+) and N-methyl-D-glucamine (NMDG(+)) showed enhanced activation and current facilitation following cholesterol depletion. This contrasts with the inhibitory effect of methyl-β-cyclodextrin reported for other P2X subtypes. Mutational analysis suggests the involvement of an N-terminal region and a proximal C-terminal region that comprises multiple cholesterol recognition amino acid consensus (CRAC) motifs, in the cholesterol sensitivity of channel gating. These results reveal cholesterol as a negative regulator of P2X7 receptor pore formation, protecting cells from P2X7-mediated cell death.
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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.