ArticleThe Journal of physiology2006
Regulation of the desensitization and ion selectivity of ATP-gated P2X2 channels by phosphoinositides.
Article in The Journal of physiology, 2006. 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, 78 citations in OpenAlex.
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.Science advances · 2026Article
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.bioRxiv : the preprint server for biology · 2025Article
- Combining native mass spectrometry and lipidomics to uncover specific membrane protein-lipid interactions from natural lipid sources.Chemical science · 2023Article
- PI(4,5)P2-dependent and -independent roles of PI4P in the control of hormone secretion by pituitary cells.Frontiers in endocrinology · 2023Review
- Entropy in the Molecular Recognition of Membrane Protein-Lipid Interactions.The journal of physical chemistry letters · 2021Article
- Insight into the Phospholipid-Binding Preferences of Kir3.4.Biochemistry · 2021Article
- Selective binding of a toxin and phosphatidylinositides to a mammalian potassium channel.Nature communications · 2019Article
- Organization of ATP-gated P2X1 receptor intracellular termini in apo and desensitized states.The Journal of general physiology · 2019Article
- Opposing Roles of Calcium and Intracellular ATP on Gating of the Purinergic P2X2 Receptor Channel.International journal of molecular sciences · 2018Article
- Allostery revealed within lipid binding events to membrane proteins.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Novel channel-mediated choline transport in cholinergic neurons of the mouse retina.Journal of neurophysiology · 2017Article
- Co-localization of Pirt protein and P2X2 receptors in the mouse enteric nervous system.Purinergic signalling · 2016Article
- Phosphoinositide signaling in somatosensory neurons.Advances in biological regulation · 2016Review
- Characterization of ATPase Activity of P2RX2 Cation Channel.Frontiers in physiology · 2016Article
- Properties of ATP-gated ion channels assembled from P2X2 subunits in mouse cochlear Reissner's membrane epithelial cells.Purinergic signalling · 2015Article
- Phosphoinositides regulate ion channels.Biochimica et biophysica acta · 2015Review
- Use of chimeras, point mutants, and molecular modeling to map the antagonist-binding site of 4,4',4″,4‴-(carbonylbis-(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakisbenzene-1,3-disulfonic acid (NF449) at P2X1 receptors for ATP.The Journal of biological chemistry · 2015Article
- Key sites for P2X receptor function and multimerization: overview of mutagenesis studies on a structural basis.Current medicinal chemistry · 2015Review
- On-site energy supply at synapses through monocarboxylate transporters maintains excitatory synaptic transmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphoinositides (PIP(n)s) are known to regulate the activity of some ion channels. Here we determined that ATP-gated P2X(2) channels also are regulated by PIP(n)s, and investigated the structural background and the unique features of this regulation. We initially used two-electrode voltage clamp to analyse the electrophysiological properties of P2X(2) channels expressed in Xenopus oocytes, and observed that preincubation with wortmannin or LY294002, two PI3K inhibitors, accelerated channel desensitization. K365Q or K369Q mutation of the conserved, positively charged, amino acid residues in the proximal region of the cytoplasmic C-terminal domain also accelerated desensitization, whereas a K365R or K369R mutation did not. We observed that the permeability of the channel to N-methyl-d-glucamine (NMDG) transiently increased and then decreased after ATP application, and that the speed of the decrease was accelerated by K365Q or K369Q mutation or PI3K inhibition. Using GST-tagged recombinant proteins spanning the proximal C-terminal region, we then analysed their binding of the P2X(2) cytoplasmic domain to anionic lipids using PIP(n)s-coated nitrocellulose membranes. We found that the recombinant proteins that included the positively charged region bound to PIPs and PIP(2)s, and that this binding was eliminated by the K365Q and K369Q mutations. We also used a fluorescence assay to confirm that fusion proteins comprising the proximal C-terminal region of P2X(2) with EGFP expressed in COS-7 cells closely associated with the membrane. Taken together, these results show that membrane-bound PIP(n)s play a key role in maintaining channel activity and regulating pore dilation through electrostatic interaction with the proximal region of the P2X(2) cytoplasmic C-terminal domain.
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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 OpenQuestion graph.