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Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila


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 cues1,2. Many TRPs are multimodal receptors that respond to diverse stimuli1,2,3, 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 chemicals4 and innocuous warming5, 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.

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Figure 1: TRPA1-dependent gustatory neurons do not respond to heat.
Figure 2: TRPA1 isoform diversity yields tissue-specific channels with different thermal sensitivities.
Figure 3: TRPA1 isoform diversity determines sensory specificity of gustatory neurons.
Figure 4: Regulation of insect TRPA1 thermosensitivity by alternative N termini.

Accession codes

Primary accessions

NCBI Reference Sequence

Data deposits

TRPA1(A) sequence is deposited in GenBank under accession number JQ015263.


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We thank the P.A.G. laboratory, H. Garrity, L. Griffith, L. Huang, J. Rodriguez and M. Rosbash for helpful comments, and F. Marion-Poll and A. Dahanukar for guidance with tip-recording. This work was supported by grants from the National Science Foundation (IOS-1025307), National Institute of Mental Health (EUREKA R01 MH094721) and National Institute of Neurological Disorders and Stroke (NINDS) (PO1 NS044232) to P.A.G., a National Research Service Award from NINDS to V.C.P. (F31 NS071897-02) and the Boston College DeLuca Professorship to M.A.T.M.

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Authors and Affiliations



K.K., V.C.P. and P.A.G. designed experiments. K.K. performed molecular biology, genetics and oocyte physiology. V.C.P. performed genetics and sensory neuron electrophysiology. E.C.C. performed genetics and behavioural experiments. A.M.D. performed behavioural experiments. L.N. performed immunohistochemistry. A.M.J., K.R. and M.A.T.M. grew and harvested mosquitoes. P.A.G. performed bioinformatics. K.K., V.C.P. and P.A.G. wrote the paper.

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Correspondence to Paul A. Garrity.

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Supplementary Information

The file contains Supplementary Figures 1-10 with legends. (PDF 1266 kb)

Supplementary Movie 1

This movie 'warmth triggered regurgitation in a TRPA1(B) rescue fly' shows a Gr66a>TRPA1(B); TrpA1ins mutant rescue animal being heated from room temperature (~23˚C) to ~32˚C over 30 seconds. The fly responds to warming by initiating proboscis movements and eventually regurgitates previously ingested liquid. (MOV 8091 kb)

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Kang, K., Panzano, V., Chang, E. et al. Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila. Nature 481, 76–80 (2012).

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