ArticlePflugers Archiv : European journal of physiology2012
The TRPM8 ion channel comprises direct Gq protein-activating capacity.
Article in Pflugers Archiv : European journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Cold receptor TRPM8 as a target for migraine-associated pain and affective comorbidities.The journal of headache and pain · 2025Article
- Stimulus-Transcription Coupling of TRPM3 Channels: A Signaling Pathway from the Plasma Membrane to the Nucleus.Biomolecules · 2025Review
- Signal Transduction of Transient Receptor Potential TRPM8 Channels: Role of PIP5K, Gq-Proteins, and c-Jun.Molecules (Basel, Switzerland) · 2024Article
- The Effect of Menthol Mouth Rinsing and Fluid Temperature on Male Cycling Performance in Thermoneutral Conditions.Nutrients · 2024Article
- Intracellular CaFrontiers in physiology · 2023Review
- Mutations of TRPM8 channels: Unraveling the molecular basis of activation by cold and ligands.Medicinal research reviews · 2022Review
- Article
- The cool things to know about TRPM8!Channels (Austin, Tex.) · 2020Review
- Molecular basis of peripheral innocuous cold sensitivity.Handbook of clinical neurology · 2018Review
- TRPM8 inhibits endothelial cell migration via a non-channel function by trapping the small GTPase Rap1.The Journal of cell biology · 2017Article
- Ion channel mechanisms of rat tail artery contraction-relaxation by menthol involving, respectively, TRPM8 activation and L-type Ca2+ channel inhibition.American journal of physiology. Heart and circulatory physiology · 2016Article
- TRPM8: a potential target for cancer treatment.Journal of cancer research and clinical oncology · 2016Review
- Phospholipase C δ4 regulates cold sensitivity in mice.The Journal of physiology · 2016Article
- Integration of Fourier Transform Infrared Spectroscopy, Fluorescence Spectroscopy, Steady-state Kinetics and Molecular Dynamics Simulations of Gαi1 Distinguishes between the GTP Hydrolysis and GDP Release Mechanism.The Journal of biological chemistry · 2015Article
- The puzzle of TRPV4 channelopathies.EMBO reports · 2013Review
- Article
- Direct inhibition of the cold-activated TRPM8 ion channel by Gαq.Nature cell biology · 2012Article
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transient receptor potential (TRP) family of ion channels comprises receptors that are activated by a vast variety of physical as well as chemical stimuli. TRP channels interact in a complex manner with several intracellular signaling cascades, both up- and downstream of receptor activation. Investigating cascades stimulated downstream of the cold and menthol receptor TRPM8, we found evidence for both, functional and structural interaction of TRPM8 with Gαq. We demonstrated menthol-evoked increase in intracellular Ca(2+) under extracellular Ca(2+)-free conditions, which was blocked by the PLC inhibitors U73122 or edelfosine. This metabotropic Ca(2+) signal could be observed also in cells expressing a channel-dead (i.e. non-conducting) or a chloride-conducting TRPM8 pore mutant. However, this intracellular metabotropic Ca(2+) signal could not be detected in Gαq deficient cells or in the presence of dominant-negative GαqX. Evidence for a close spatial proximity necessary for physical interaction of TRPM8 and Gαq was provided by acceptor bleaching experiments demonstrating FRET between TRPM8-CFP and Gαq-YFP. A Gαq-YFP mobility assay (FRAP) revealed a restricted diffusion of Gαq-YFP under conditions when TRPM8 is immobilized in the plasma membrane. Moreover, a menthol-induced and TRPM8-mediated G protein activation could be demonstrated by FRET experiments monitoring the dissociation of Gαq-YFP from a Gβ/Gγ-CFP complex, and by the exchange of radioactive [(35)S]GTPγS for GDP. Our observations lead to a view that extends the operational range of the TRPM8 receptor from its function as a pure ion channel to a molecular switch with additional metabotropic capacity.
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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.