ArticleScientific reports2016
N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Functions of TRPs in retinal tissue in physiological and pathological conditions.Frontiers in molecular neuroscience · 2024Review
- The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024Review
- Human Transient Receptor Potential Ankyrin 1 Channel: Structure, Function, and Physiology.Sub-cellular biochemistry · 2024Review
- TRP channels: a journey towards a molecular understanding of pain.Nature reviews. Neuroscience · 2022Review
- Regulation of transient receptor potential channels by traditional Chinese medicines and their active ingredients.Frontiers in pharmacology · 2022Review
- Protocols for Characterization of Cdk5 Kinase Activity.Current protocols · 2021Article
- Functional evidence of distinct electrophile-induced activation states of the ion channel TRPA1.Biochemistry and biophysics reports · 2021Article
- Transient receptor potential ankyrin 1 channel: An evolutionarily tuned thermosensor.Physiological research · 2021Review
- Phospho-Mimetic Mutation at Ser602 Inactivates Human TRPA1 Channel.International journal of molecular sciences · 2020Article
- Proximal C-Terminus Serves as a Signaling Hub for TRPA1 Channel Regulation via Its Interacting Molecules and Supramolecular Complexes.Frontiers in physiology · 2020Article
- Acute exposure to high-induction electromagnetic field affects activity of model peripheral sensory neurons.Journal of cellular and molecular medicine · 2018Article
- Phosphorylation of the Transient Receptor Potential Ankyrin 1 by Cyclin-dependent Kinase 5 affects Chemo-nociception.Scientific reports · 2018Article
- Modulation of TRPA1 channel activity by Cdk5 in sensory neurons.Channels (Austin, Tex.) · 2018Article
- Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons.Molecular painArticle
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human transient receptor potential ankyrin channel 1 (TRPA1) is a polymodal sensor implicated in pain, inflammation and itching. An important locus for TRPA1 regulation is the cytoplasmic N-terminal domain, through which various exogenous electrophilic compounds such as allyl-isothiocyanate from mustard oil or cinnamaldehyde from cinnamon activate primary afferent nociceptors. This major region is comprised of a tandem set of 17 ankyrin repeats (AR1-AR17), five of them contain a strictly conserved T/SPLH tetrapeptide motif, a hallmark of an important and evolutionarily conserved contribution to conformational stability. Here, we characterize the functional consequences of putatively stabilizing and destabilizing mutations in these important structural units and identify AR2, AR6, and AR11-13 to be distinctly involved in the allosteric activation of TRPA1 by chemical irritants, cytoplasmic calcium, and membrane voltage. Considering the potential involvement of the T/SP motifs as putative phosphorylation sites, we also show that proline-directed Ser/Thr kinase CDK5 modulates the activity of TRPA1, and that T673 outside the AR-domain is its only possible target. Our data suggest that the most strictly conserved N-terminal ARs define the energetics of the TRPA1 channel gate and contribute to chemical-, calcium- and voltage-dependence.
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