Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila

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, TRP channels are key transducers of thermal, chemical and other sensory cues1, 2. Many TRPs are multi-modal receptors that respond to diverse stimuli1–3, but how animals distinguish sensory inputs activating the same TRP is largely unknown. Here we determine how stimuli activating Drosophila TRPA1 are discriminated. While 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, suggesting 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 where thermal sensitivity can be maladaptive.

Drosophila TRPA1 isoforms detect UV light via photochemical production of H 2 O 2

“…We found that ectopic expression of these H 2 O 2 -sensitive dTRPA1 isoforms conferred UV sensitivity to light-insensitive cultured HEK293 cells and a few types of light-insensitive Drosophila neurons. The light and H 2 O 2 sensitivities are specific to certain dTRPA1 isoforms, consistent with previous findings that different dTRPA1 isoforms exhibit distinct thermal sensitivities (20,21). Strikingly, the H 2 O 2 -sensitive dTRPA1 was as effective as channelrhodopsin-2 (ChR2) in triggering light-produced motor responses when expressed in a specific group of motor neurons that control proboscis extension…”

“…Animals were raised in standard molasses/cornmeal/yeast/agar food and maintained in a Darwin Chamber with temperature set at 25°C and humidity level at 60-65%. The stocks used were as follows: w 1118 , UAS-GCaMP3 (BL-32236), UAS-GCaMP6 (BL-42746), UAS-ChR2-YFP, E49-GAL4 (31), AKH-GAL4 (BL-25684), dTRPA1 KO (27), Gr28b PBac01884 (BL-10743), Gr28b Df(2L)7031 /CyO (BL-7804), norpA 36 (BL-9048), santa-maria (BL-24520), UAS-dTRPA1-RNAi (27), UAS-DUOX-RNAi 1 (BL-32903), UAS-cat (BL-24621), ILP7-GAL4 (44), UAS-dTRPA1(A)10b (21), UAS-dTRPA1(B)10a (20), ppk1-GAL4 (45), UAS-dTRPA1(A)10a (this work), UAS-mTRPA1 (a gift from J. Grandl, Department of Neurobiology, Duke University, Durham, NC).…”

“…Our results suggest specific H 2 O 2 -sensitive TRPA1 isoforms can be activated by UV via a photochemical transduction cascade and that these isoforms may be exploited as a UV-dependent optogenetic tool for controlling neuronal activities. (20,21) (Fig. 1A).…”

“…Indeed, a recent finding has suggested that two specific GPCRs-GUR-3 and LITE-1-both of which play important roles in light sensing in C. elegans, may also be H 2 O 2 sensitive (16). Moreover, TRPA1, an evolutionarily conserved TRP channel known for its role in sensing many chemical irritants, has been shown to sense H 2 O 2 (17)(18)(19)(20)(21)(22)(23)(24), thus TRPA1 may be activated by light via sensing light-induced H 2 O 2 production. Some recent evidence has demonstrated a role for TRPA1 in light sensing.…”

A Bitter Taste of the Sun Makes Egg-Laying Flies Run

“…How does the same channel distinguish different types of stimuli? At least in Drosophila, this is achieved through alternative exon usage (Kang et al 2012). Chemosensory and thermosensitive TRPA1 channels arise from distinct isoforms that contain different N-terminal sequences.…”