title: Thermosensory and nonthermosensory isoforms of Drosophila melanogaster TRPA1 reveal heat-sensor domains of a thermoTRP Channel.
abstract: Specialized somatosensory neurons detect temperatures ranging from pleasantly cool or warm to burning hot and painful (nociceptive). The precise temperature ranges sensed by thermally sensitive neurons is determined by tissue-specific expression of ion channels of the transient receptor potential(TRP) family.We show here that in Drosophila, TRPA1 is required for the sensing of nociceptive heat. We identify two previously unidentified protein isoforms of dTRPA1, named dTRPA1-C and dTRPA1-D, that explain this requirement. A dTRPA1-C/D reporter was exclusively expressed in nociceptors, and dTRPA1-C rescued thermal nociception phenotypes when restored to mutant nociceptors. However,surprisingly, we find that dTRPA1-C is not a direct heat sensor. Alternative splicing generates at least four isoforms of dTRPA1. Our analysis of these isoforms reveals a 37-amino-acid-long intracellular region (encoded by a single exon) that is critical for dTRPA1 temperature responses. The identification of these amino acids opens the door to a biophysical understanding of a molecular thermosensor.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Lixian
authors.initials: L
authors.lastname: Zhong
authors.forename: Andrew
authors.initials: A
authors.lastname: Bellemer
authors.forename: Haidun
authors.initials: H
authors.lastname: Yan
authors.forename: Honjo
authors.initials: H
authors.lastname: Ken
authors.forename: Robertson
authors.initials: R
authors.lastname: Jessica
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Hwang
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Pitt
authors.forename: W Daniel
authors.initials: WD
authors.lastname: Tracey
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005820:Genetic Testing; D006358:Hot Temperature; D015640:Ion Channel Gating; D007473:Ion Channels; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D059225:Nociception; D009619:Nociceptors / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000737:chemistry* / Q000378:metabolism*; D013697:Thermosensing
chemical_list: D029721:Drosophila Proteins; D007473:Ion Channels; D020033:Protein Isoforms; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C475684:TrpA1 protein, Drosophila