The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
TRPV1 Channels Are Intrinsically Heat Sensitive and Negatively Regulated by Phosphoinositide Lipids
Open accessAbstract
Summary The capsaicin receptor, TRPV1, is regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), although the precise nature of this effect (i.e., positive or negative) remains controversial. Here, we reconstitute purified TRPV1 into artificial liposomes, where it is gated robustly by capsaicin, protons, spider toxins and, notably, heat, demonstrating intrinsic sensitivity of the channel to both chemical and thermal stimuli. TRPV1 is fully functional in the absence of phosphoinositides, arguing against their proposed obligatory role in channel activation. Rather, introduction of various phosphoinositides, including PIP2, PI4P and PI, inhibits TRPV1, supporting a model whereby phosphoinositide turnover contributes to thermal hyperalgesia by disinhibiting the channel. Using an orthogonal chemical strategy, we show that association of the TRPV1 C-terminus with the bilayer modulates channel gating, consistent with phylogenetic data implicating this domain as a key regulatory site for tuning stimulus sensitivity. Beyond TRPV1, these findings are relevant to understanding how membrane lipids modulate other “receptor-operated” TRP channels.
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Self-citationThe Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli
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Self-citationVanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
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Self-citationAN INTRODUCTION TO TRP CHANNELS
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Molecular Basis for Species-Specific Sensitivity to “Hot” Chili Peppers
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Self-citationInduction of vanilloid receptor channel activity by protein kinase C
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Cited by
Phosphoinositides regulate ion channels
Hille, B., Dickson, E. J., Kruse, M., Vivas, O., & Suh, B.-C. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.09.010 · Cited by 312
Nerve Growth Factor and Pain Mechanisms
Denk, F., Bennett, D. L., & McMahon, S. B. (2017) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-072116-031121 · Cited by 257
Garami, A., Shimansky, Y. P., Rumbus, Z., Vizin, R. C. L., Farkas, N., Hegyi, J., Szakacs, Z., Solymar, M., Csenkey, A., Chiche, D. A., et al. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107474 · Cited by 159
Lipid agonism: The PIP2 paradigm of ligand-gated ion channels
Hansen, S. B. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2015.01.011 · Cited by 146
Tools for Understanding Nanoscale Lipid Regulation of Ion Channels
Robinson, C. V., Rohacs, T., & Hansen, S. B. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.04.001 · Cited by 85
Metadata
- Authors
- Cao, E., Cordero-Morales, J. F., Liu, B., Qin, F., & Julius, D.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 77
- Issue
- 4
- Pages
- 667-679
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2029360579
- Cited by
- 340
- References
- 70
- FWCI
- 19.21
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Cao, E., Cordero-Morales, J. F., Liu, B., Qin, F., & Julius, D. (2013). TRPV1 Channels Are Intrinsically Heat Sensitive and Negatively Regulated by Phosphoinositide Lipids. Neuron. https://doi.org/10.1016/j.neuron.2012.12.016
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