Nucleophile sensitivity of Drosophila TRPA1 underlies light-induced feeding deterrence

Abstract

Solar irradiation including ultraviolet (UV) light causes tissue damage by generating reactive free radicals that can be electrophilic or nucleophilic due to unpaired electrons. Little is known about how free radicals induced by natural sunlight are rapidly detected and avoided by animals. We discover that Drosophila Transient Receptor Potential Ankyrin 1 (TRPA1), previously known only as an electrophile receptor, sensitively detects photochemically active sunlight through nucleophile sensitivity. Rapid light-dependent feeding deterrence in Drosophila was mediated only by the TRPA1(A) isoform, despite the TRPA1(A) and TRPA1(B) isoforms having similar electrophile sensitivities. Such isoform dependence re-emerges in the detection of structurally varied nucleophilic compounds and nucleophilicity-accompanying hydrogen peroxide (H2O2). Furthermore, these isoform-dependent mechanisms require a common set of TRPA1(A)-specific residues dispensable for electrophile detection. Collectively, TRPA1(A) rapidly responds to natural sunlight intensities through its nucleophile sensitivity as a receptor of photochemically generated radicals, leading to an acute light-induced behavioral shift in Drosophila.DOI: http://dx.doi.org/10.7554/eLife.18425.001

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

“…By contrast, dTrpA1-mediated activation of bitter GRNs in response to UV is likely to trigger avoidance regardless of egg-laying state. This idea is borne out by the findings of an independent study that reported dTrpA1-dependent feeding deterrence in bright light (Du et al 2016), and consistent with the observation that UV-sensitive dTrpA1 is also expressed in bitter GRNs in male flies. Interestingly, bitter tastants tested in similar egg-laying assays are either selected or disfavored depending on the nature of the alternative that is presented (Yang et al 2008).…”

“…Bitter GRNs in the proboscis, expressing UV-sensitive dTrpA1, do so in the taste system (Guntur et al 2016). Several recent findings suggest that bitter GRNs function as polymodal sensory neurons whose activation triggers avoidance to multiple aversive stimuli (Kim et al 2010;Weiss et al 2011;Du et al 2015Du et al , 2016Soldano et al 2016), similar to the polymodal UV-sensitive nociceptive neurons in larvae (Hwang et al 2007;Xiang et al 2010). How then does the gustatory sensor coordinate with the visual sensors in controlling behavioral responses to UV?…”

Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for animal nociception

“…Hydrogen peroxide (H 2 O 2 ), is amongst the earliest known markers of mechanical tissue damage in vertebrates 33 , Drosophila 34 as well as Planarians 35 . H 2 O 2 is a well-known activator of mammalian and Drosophila TRPA1 ( 36–39 , together with additional Reactive Oxygen Species –ROS 40 ), and recent work suggest that responses to potentially damaging short-wavelength UV light occurs through photochemical production of H 2 O 2 , and requires TRPA1 in both flies 37–39,41 and planarians 42 . Thus, if noxious heat were to cause rapid, localized, production of H 2 O 2 /ROS, this could provide the direct signal for TRPA1 activation that mediates nociceptive responses.…”

Analysis of phototoxin taste closely correlates nucleophilicity to type 1 phototoxicity

“…In contrast, TRPA1(A) has been recently characterized as an ion channel receptor for nucleophilic compounds. One implication of its nucleophile sensitivity was found in UV-dependent feeding deterrence, where UV-induced free radicals and reactive oxygen species activate TRPA1(A) in bitter gustatory receptor neurons via nucleophile sensitivity of the channel (13). Here, we find that TRPA1(A), which acts as a receptor for radicals generated after light illumination, aphotically detects polycyclic phototoxins, which are capable of radical and reactive oxygen species generation on light illumination.…”