ArticleThe Journal of biological chemistry2008
Determinants of molecular specificity in phosphoinositide regulation. Phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) is the endogenous lipid regulating TRPV1.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 109 citations in OpenAlex.
- Review
- Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A.Nature communications · 2023Article
- Current advancements and future perspectives of long noncoding RNAs in lipid metabolism and signaling.Journal of advanced research · 2023Review
- Negative self-regulation of transient receptor potential canonical 4 by the specific interaction with phospholipase C-δ1.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- Regulation of ThermoTRP Channels by PIP2 and Cholesterol.Advances in experimental medicine and biology · 2023Article
- TRP channels: a journey towards a molecular understanding of pain.Nature reviews. Neuroscience · 2022Review
- Impact of the Protonation State of Phosphatidylinositol 4,5-Bisphosphate (PIP2) on the Binding Kinetics and Thermodynamics to Transient Receptor Potential Vanilloid (TRPV5): A Milestoning Study.The journal of physical chemistry. B · 2021Article
- Deficiency of Inositol Monophosphatase Activity Decreases Phosphoinositide Lipids and Enhances TRPV1 FunctionThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Methods to study phosphoinositide regulation of ion channels.Methods in enzymology · 2021Article
- Evidence that the TRPV1 S1-S4 membrane domain contributes to thermosensing.Nature communications · 2020Article
- Structural insights into the gating mechanisms of TRPV channels.Cell calcium · 2020Review
- Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2.Structure (London, England : 1993) · 2020Article
- TRP ion channels: Proteins with conformational flexibility.Channels (Austin, Tex.) · 2019Review
- With PIPs, you get ZIPs and blips.The Journal of general physiology · 2019Article
- Structures of TRPV2 in distinct conformations provide insight into role of the pore turret.Nature structural & molecular biology · 2019Article
- Regulation of thermoTRPs by lipids.Temperature (Austin, Tex.) · 2017Review
- Exploring functional roles of TRPV1 intracellular domains with unstructured peptide-insertion screening.Scientific reports · 2016Article
- TRPV1: A Target for Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2016Review
- A molecular determinant of phosphoinositide affinity in mammalian TRPV channels.Scientific reports · 2016Article
- Phosphoinositide signaling in somatosensory neurons.Advances in biological regulation · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Once thought of as simply an oily barrier that maintains cellular integrity, lipids are now known to play an active role in a large variety of cellular processes. Phosphoinositides are of particular interest because of their remarkable ability to affect many signaling pathways. Ion channels and transporters are an important target of phosphoinositide signaling, but identification of the specific phosphoinositides involved has proven elusive. TRPV1 is a good example; although phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P(2)) can potently regulate its activation, we show that phosphatidylinositol (4)-phosphate (PI(4)P) and phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P(3)) can as well. To determine the identity of the endogenous phosphoinositide regulating TRPV1, we applied recombinant pleckstrin homology domains to inside-out excised patches. Although a PI(4,5)P(2)-specific pleckstrin homology domain inhibited TRPV1, a PI(3,4,5)P(3)-specific pleckstrin homology domain had no effect. Simultaneous confocal imaging and electrophysiological recording of whole cells expressing a rapamycin-inducible lipid phosphatase also demonstrates that depletion of PI(4,5)P(2) inhibits capsaicin-activated TRPV1 current; the PI(4)P generated by the phosphatases was not sufficient to support TRPV1 function. We conclude that PI(4,5)P(2), and not other phosphoinositides or other lipids, is the endogenous phosphoinositide regulating TRPV1 channels.
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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.