Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila

Abstract

Many TRP ion channels respond to more than one category of cue, and how they discriminate between them is largely unknown; the mechanism by which TRPA1 discriminates between sensory stimuli in Drosophila is now determined. How an animal can discriminate between two different signals that activate the same molecular detector is a fundamental question in signalling specificity. The ion channels of the TRP family provide notable examples of the phenomenon, such as TRPA1, which responds to both noxious chemicals and innocuous warming. Paul Garrity and colleagues report that Drosophila chemosensory neurons produce a TRPA1 variant with reduced thermosensitivity, which restricts aversive behavioural responses to harmful chemicals. A similar pattern of TRPA1 isoform diversity occurs in malaria mosquitoes, which suggests that cell-type segregation may help them to discriminate between host-derived warmth and chemical repellents. 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.