ArticleThe Journal of biological chemistry2014
Bidirectional modulation of thermal and chemical sensitivity of TRPM8 channels by the initial region of the N-terminal domain.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Modulation of transient receptor potential (TRP) channels by plant derived substances used in over-the-counter cough and cold remedies.Respiratory research · 2023Pooled it
- Bryostatins 1 and 3 inhibit TRPM8 and modify TRPM8- and TRPV1-mediated lung epithelial cell responses to a proinflammatory stimulus via protein kinase C.Molecular pharmacology · 2025Article
- A new gene for autosomal dominant facial palsy/migraine identified in a family by whole exome sequencing.European journal of neurology · 2024Article
- Molecular determinants of TRPM8 function: key clues for a cool modulation.Frontiers in pharmacology · 2023Review
- Validation of Six Commercial Antibodies for the Detection of Heterologous and Endogenous TRPM8 Ion Channel Expression.International journal of molecular sciences · 2022Article
- Mutations of TRPM8 channels: Unraveling the molecular basis of activation by cold and ligands.Medicinal research reviews · 2022Review
- On the modulation of TRPM channels: Current perspectives and anticancer therapeutic implications.Frontiers in oncology · 2022Review
- Constitutive Phosphorylation as a Key Regulator of TRPM8 Channel Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation.International journal of molecular sciences · 2021Review
- Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [CaNeurology. Genetics · 2021Article
- Negative Modulation of TRPM8 Channel Function by Protein Kinase C in Trigeminal Cold Thermoreceptor Neurons.International journal of molecular sciences · 2020Article
- Critical role of the pore domain in the cold response of TRPM8 channels identified by ortholog functional comparison.The Journal of biological chemistry · 2018Article
- Sex differences in mouse Transient Receptor Potential Cation Channel, Subfamily M, Member 8 expressing trigeminal ganglion neurons.PloS one · 2017Article
- Article
- Comparative genomic analyses reveal a vast, novel network of nucleotide-centric systems in biological conflicts, immunity and signaling.Nucleic acids research · 2015Article
- Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as 'well expressed', 'poorly expressed' or 'salvageable'.Bioscience reports · 2015Article
- Trafficking of ThermoTRP Channels.Membranes · 2014Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TRPM8, a nonselective cation channel activated by cold, voltage, and cooling compounds such as menthol, is the principal molecular detector of cold temperatures in primary sensory neurons of the somatosensory system. The N-terminal domain of TRPM8 consists of 693 amino acids, but little is known about its contribution to channel function. Here, we identified two distinct regions within the initial N terminus of TRPM8 that contribute differentially to channel activity and proper folding and assembly. Deletion or substitution of the first 40 residues yielded channels with augmented responses to cold and menthol. The thermal threshold of activation of these mutants was shifted 2 °C to higher temperatures, and the menthol dose-response curve was displaced to lower concentrations. Site-directed mutagenesis screening revealed that single point mutations at positions Ser-26 or Ser-27 by proline caused a comparable increase in the responses to cold and menthol. Electrophysiological analysis of the S27P mutant revealed that the enhanced sensitivity to agonists is related to a leftward shift in the voltage dependence of activation, increasing the probability of channel openings at physiological membrane potentials. In addition, we found that the region encompassing positions 40-60 is a key element in the proper folding and assembly of TRPM8. Different deletions and mutations within this region rendered channels with an impaired function that are retained within the endoplasmic reticulum. Our results suggest a critical contribution of the initial region of the N-terminal domain of TRPM8 to thermal and chemical sensitivity and the proper biogenesis of this polymodal ion channel.
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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.