PMID:22139422

Citation	Kang, K, Panzano, VC, Chang, EC, Ni, L, Dainis, AM, Jenkins, AM, Regna, K, Muskavitch, MA and Garrity, PA (2012) Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila. Nature 481:76-80
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.
Links	PubMed PMC3272886 Online version:10.1038/nature10715
Keywords	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; Molecular Sequence Data; Oocytes; Organ Specificity; Protein Isoforms/chemistry; Protein Isoforms/genetics; Protein Isoforms/metabolism; Sensory Receptor Cells/metabolism; Sequence Alignment; Signal Transduction; TRPC Cation Channels/chemistry; TRPC Cation Channels/genetics; TRPC Cation Channels/metabolism; Xenopus laevis
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
DROME:TRPA1		GO:0043052: thermotaxis	ECO:0000315:		P		Figure 3 references differing sensitivity to warmth in TrpA1 mutants	complete CACAO 5192
DROME:G9L8C4		GO:0009408: response to heat	ECO:0000315:		P		Figure 4 references mutating either a cysteine (C105) or two basic residues (R113, R116) in TRPA1(A) markedly increased temperature responsiveness (Fig. 4a–c and Supplementary Figs 6 and 7). The temperatures used were from 27–37 degrees C (warming).	complete CACAO 5312
DROME:G9L8C4	involved_in	GO:0009408: response to heat	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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