The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Identification of Transmembrane Domain 5 as a Critical Molecular Determinant of Menthol Sensitivity in Mammalian TRPA1 Channels
Open accessAbstract
TRPA1 is a member of the transient receptor potential (TRP) family of ion channels and is expressed in a subset of nociceptive neurons. An increasing body of evidence suggests that TRPA1 functions as a chemical nocisensor for a variety of reactive chemicals, such as pungent natural compounds and environmental irritants. Activation of TRPA1 by reactive compounds has been demonstrated to be mediated through covalent modification of cytoplasmic cysteines located in the N terminus of the channel, rather than classical lock-and-key binding. TRPA1 activity is also modulated by numerous nonreactive chemicals, but the underlying mechanism is unknown. Menthol, a natural nonreactive cooling compound, is best known as an activator of TRPM8, a related TRP ion channel required for cool thermosensation in vivo. More recently, menthol has been shown to be an activator of mouse TRPA1 at low concentrations, and a blocker, at high concentrations. Here, we show that human TRPA1 is only activated by menthol, whereas TRPA1 from nonmammalian species are insensitive to menthol. Mouse-human TRPA1 chimeras reveal the pore region [including transmembrane domain 5 (TM5) and TM6] as the critical domain determining whether menthol can act as an inhibitor. Furthermore, chimeras between Drosophila melanogaster and mammalian TRPA1 highlight specific residues within TM5 critical for menthol responsiveness. Interestingly, this TM5 region also determines the sensitivity of TRPA1 to other chemical modulators. These data suggest separable structural requirements for modulation of TRPA1 by covalent and nonreactive molecules. Whether this region is involved in binding or gating of TRPA1 channels is discussed.
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Scalable molecular dynamics with NAMD
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The Structure of the Potassium Channel: Molecular Basis of K + Conduction and Selectivity
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Identification of a cold receptor reveals a general role for TRP channels in thermosensation
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ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures
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A TRP Channel that Senses Cold Stimuli and Menthol
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TRPA1 Mediates the Inflammatory Actions of Environmental Irritants and Proalgesic Agents
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Cited by
A Gain-of-Function Mutation in TRPA1 Causes Familial Episodic Pain Syndrome
Kremeyer, B., Lopera, F., Cox, J. J., Momin, A., Rugiero, F., Marsh, S., Woods, C. G., Jones, N. G., Paterson, K. J., Fricker, F. R., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.04.030 · Cited by 443
TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain
Liu, B., Fan, L., Balakrishna, S., Sui, A., Morris, J. B., & Jordt, S.-E. (2013) · Pain · doi:10.1016/j.pain.2013.06.043 · Cited by 319
The thermo‐TRP ion channel family: properties and therapeutic implications
Vay, L., Gu, C., & McNaughton, P. A. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01601.x · Cited by 296
Nicotine activates the chemosensory cation channel TRPA1
Talavera, K., Gees, M., Karashima, Y., Meseguer, V. M., Vanoirbeek, J. A. J., Damann, N., Everaerts, W., Benoit, M., Janssens, A., Vennekens, R., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2379 · Cited by 259
TRPA1 channels: molecular sentinels of cellular stress and tissue damage
Viana, F. (2016) · The Journal of Physiology · doi:10.1113/jp270935 · Cited by 210
Metadata
- Authors
- Xiao, B., Dubin, A. E., Bursulaya, B., Viswanath, V., Jegla, T. J., & Patapoutian, A.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-09-24
- Volume
- 28
- Issue
- 39
- Pages
- 9640-9651
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W1978128137
- Cited by
- 321
- References
- 50
- FWCI
- 6.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Xiao, B., Dubin, A. E., Bursulaya, B., Viswanath, V., Jegla, T. J., & Patapoutian, A. (2008). Identification of Transmembrane Domain 5 as a Critical Molecular Determinant of Menthol Sensitivity in Mammalian TRPA1 Channels. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.2772-08.2008
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