title: Ligand stoichiometry of the cold- and menthol-activated channel TRPM8.
abstract: Temperature-sensitive transient receptor potential (TRP) channels play a key role in somatosensation, not only as primary thermosensors but also as chemosensors for various compounds that evoke a thermal sensation. The fundamental mechanisms whereby TRP channels translate ligand binding into opening of the ion conducting pore are, however, poorly understood, and the actual number of ligands that bind to these channels is fully unknown. Here, we investigated the ligand stoichiometry of the cold sensor and menthol receptor TRPM8. Based on a detailed biophysical analysis of tandem constructs of wild-type and menthol-insensitive TRPM8 subunits, we now provide direct evidence that each channel has four independent and energetically equivalent menthol interaction sites. These results suggest a fundamentally different ligand stoichiometry in TRP channels, in comparison with other major families of ligand-gated ion channels.
authors: Laboratory of Ion Channel Research and TRP Research Platform Leuven, KU Leuven, Herestraat 49 bus 802, B-3000 Leuven, Belgium.
authors: Annelies
authors: A
authors: Janssens
authors: Thomas
authors: T
authors: Voets
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D003080:Cold Temperature; D006801:Humans; D008024:Ligands; D008564:Membrane Potentials; D008610:Menthol / Q000378:metabolism*; D009154:Mutation; D018408:Patch-Clamp Techniques; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D008024:Ligands; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D008610:Menthol; D002118:Calcium