Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila

Nature. 2011 Dec 4;481(7379):76-80. doi: 10.1038/nature10715.

Abstract

Discriminating among sensory stimuli is critical for animal survival. This discrimination is particularly essential when evaluating whether a stimulus is noxious or innocuous. From insects to humans, transient receptor potential (TRP) channels are key transducers of thermal, chemical and other sensory cues. Many TRPs are multimodal receptors that respond to diverse stimuli, but how animals distinguish sensory inputs activating the same TRP is largely unknown. Here we determine how stimuli activating Drosophila TRPA1 are discriminated. Although Drosophila TRPA1 responds to both noxious chemicals and innocuous warming, we find that TRPA1-expressing chemosensory neurons respond to chemicals but not warmth, a specificity conferred by a chemosensory-specific TRPA1 isoform with reduced thermosensitivity compared to the previously described isoform. At the molecular level, this reduction results from a unique region that robustly reduces the channel's thermosensitivity. Cell-type segregation of TRPA1 activity is critical: when the thermosensory isoform is expressed in chemosensors, flies respond to innocuous warming with regurgitation, a nocifensive response. TRPA1 isoform diversity is conserved in malaria mosquitoes, indicating that similar mechanisms may allow discrimination of host-derived warmth--an attractant--from chemical repellents. These findings indicate that reducing thermosensitivity can be critical for TRP channel functional diversification, facilitating their use in contexts in which thermal sensitivity can be maladaptive.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • Culicidae / metabolism
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Hot Temperature*
  • Humans
  • Insect Repellents / pharmacology
  • Ion Channels
  • Molecular Sequence Data
  • Oocytes
  • Organ Specificity
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Sensory Receptor Cells / metabolism
  • Sequence Alignment
  • Signal Transduction
  • TRPA1 Cation Channel
  • TRPC Cation Channels / chemistry
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • Xenopus laevis

Substances

  • Drosophila Proteins
  • Insect Repellents
  • Ion Channels
  • Protein Isoforms
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • TrpA1 protein, Drosophila

Associated data

  • GENBANK/JQ015263