title: Residues in the pore region of Drosophila transient receptor potential A1 dictate sensitivity to thermal stimuli.
abstract: The capacity to sense temperature is essential for the survival of all animals. At the molecular level, ion channels belonging to the transient receptor potential (TRP) family of channels function as temperature sensors in animals across several phyla. TRP channels are opened directly by changes in temperature and show pronounced sensitivity at their activation range. To determine how temperature activates these channels, we analysed channels belonging to the TRPA family, which detect heat in insects and cold in mammals. By constructing chimeric proteins consisting of human and Drosophila TRPA1 channels, we mapped regions that regulate thermal activation and identified residues in the pore helix that invert temperature sensitivity of TRPA1. From analysis of individual channels we defined the gating reaction of Drosophila TRPA1 and determined how mutagenesis alters the energy landscape for channel opening. Our results reveal specific molecular requirements for thermal activation of TRPA1 and provide mechanistic insight into this process.
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Melanie
authors.initials: M
authors.lastname: Schupp
authors.forename: Sandra
authors.initials: S
authors.lastname: Zurborg
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heppenstall
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D007473:Ion Channels; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D016062:Porosity; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000737:chemistry / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D029721:Drosophila Proteins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels; C475684:TrpA1 protein, Drosophila