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A Modular PIP 2 Binding Site as a Determinant of Capsaicin Receptor Sensitivity
Abstract
The capsaicin receptor (TRPV1), a heat-activated ion channel of the pain pathway, is sensitized by phosphatidylinositol-4,5-bisphosphate (PIP 2 ) hydrolysis after phospholipase C activation. We identify a site within the C-terminal domain of TRPV1 that is required for PIP 2 -mediated inhibition of channel gating. Mutations that weaken PIP 2 -TRPV1 interaction reduce thresholds for chemical or thermal stimuli, whereas TRPV1 channels in which this region is replaced with a lipid-binding domain from PIP 2 -activated potassium channels remain inhibited by PIP 2 . The PIP 2 -interaction domain therefore serves as a critical determinant of thermal threshold and dynamic sensitivity range, tuning TRPV1, and thus the sensory neuron, to appropriately detect heat under normal or pathophysiological conditions.
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Cites
Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
Zygmunt, P. M., Petersson, J., Andersson, D. A., Chuang, H.-H., Sørgård, M., Di Marzo, V., Julius, D., & Högestätt, E. D. (1999) · Nature · doi:10.1038/22761 · Cited by 2,142
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Cited by
TRP channels as cellular sensors
Clapham, D. E. (2003) · Nature · doi:10.1038/nature02196 · Cited by 2,779
Neurotrophin-regulated signalling pathways
Reichardt, L. F. (2006) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2006.1894 · Cited by 2,195
The TRP Superfamily of Cation Channels
Montell, C. (2005) · Science's STKE · doi:10.1126/stke.2722005re3 · Cited by 989
ThermoTRP channels and beyond: mechanisms of temperature sensation
Patapoutian, A., Peier, A. M., Story, G. M., & Viswanath, V. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1141 · Cited by 873
Trp ion channels and temperature sensation
Dhaka, A., Viswanath, V., & Patapoutian, A. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112958 · Cited by 782
Metadata
- Authors
- Prescott, E. D., & Julius, D.
- Venue
- Science
- Published
- 2003-05-23
- Volume
- 300
- Issue
- 5623
- Pages
- 1284-1288
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2029993965
- Cited by
- 519
- References
- 1
- FWCI
- 19.12
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
