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Nature
2011 Dec 04;4817379:76-80. doi: 10.1038/nature10715.
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Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila.
Kang K
,
Panzano VC
,
Chang EC
,
Ni L
,
Dainis AM
,
Jenkins AM
,
Regna K
,
Muskavitch MA
,
Garrity PA
.
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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.
Figure 2. TRPA1 isoform diversity yields tissue-specific channels with different thermal sensitivitiesa,
TrpA1 gene structure and primer locations. b, Red and blue boxes denote isoform-specific sequences. a, ankyrin repeat. Dark grey, transmembrane region. c, RT-PCR. d–e, TRPA1(A)- and TRPA1(B)-dependent currents (d) and Arrhenius plots (e) in oocytes. f, Q10s from Arrhenius plot (left) or 27–37°C (right). g, h,
Left panels, NMM responsiveness of TRPA1(A) (g) and TRPA1(B) (h). Right panels, I–V relationships at points marked at left. i, Mean amplitudes at 300 µM NMM (left) and NMM dose-response (right). All data, mean +/− s.e.m. **P<0.01; n.s., not significant, t-test.
Figure 3. TRPA1 isoform diversity determines sensory specificity of gustatory neuronsa–c
TrpA1 mutant, berberine-sensitive i-type bristles expressing different TRPA1 isoforms. Responses to NMM (a) and warming (b). c, Quantitation. d–f, L-type bristles expressing TRPA1 isoforms. Responses to NMM (d) and warming (e). f, Quantitation. g, Rescue of TrpA1 mutant behavioral response to NMM-containing food. PER, proboscis extension response. h, Warmth-induced regurgitation in TrpA1 mutant rescued with TRPA1(B). i, Regurgitation upon warming from room temperature to 32°C. In c, f, g and i, statistically distinct groups marked by different letters (Tukey HSD, α = 0.01). Data are mean ± s.e.m.
Figure 4. Regulation of insect TRPA1 thermosensitivity by alternative N-terminia, TRPA1 sequence alignments. b, Q10 and transition temperatures of wild type and mutant TRPA1s. Letters denote statistically distinct groups (Tukey HSD, α = 0.02). c, Arrhenius plots of indicated channels. d,
AgTrpA1 gene structure. e, AgTRPA1 isoforms. 'a’: an ankyrin repeat. Light blue and maroon: isoform-specific amino acids. Dark grey: transmembrane region. f–h, Temperature sensitivity of AgTRPA1(A) and AgTRPA1(B). Traces (f) and Arrhenius plots (g) of temperature dependent current recordings at −60 mV in Xenopus oocytes. h, Q10s from Arrhenius plot (left) or 27–37°C (right) (**P<0.01, t-test).
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