Highlights d A given stimulus preferentially activates a single TrpA1 isoform in vivo d Polymodal nociception requires co-expression of TrpA1 isoforms in nociceptors d Each TrpA1 isoform has a unique expression profile d isoEXPRESS is a new and versatile framework targeting alternative splicing

The transient receptor potential A1 (TRPA1) channel is an evolutionarily conserved detector of temperature and irritant chemicals. Here, we show that two specific isoforms of TRPA1 in Drosophila are H 2 O 2 sensitive and that they can detect strong UV light via sensing light-induced production of H 2 O 2 . We found that ectopic expression of these H 2 O 2 -sensitive Drosophila TRPA1 (dTRPA1) isoforms conferred UV sensitivity to light-insensitive HEK293 cells and Drosophila neurons, whereas expressing the H 2 O 2 -insensitive isoform did not. Curiously, when expressed in one specific group of motor neurons in adult flies, the H 2 O 2 -sensitive dTRPA1 isoforms were as competent as the blue light-gated channelrhodopsin-2 in triggering motor output in response to light. We found that the corpus cardiacum (CC) cells, a group of neuroendocrine cells that produce the adipokinetic hormone (AKH) in the larval ring gland endogenously express these H 2 O 2 -sensitive dTRPA1 isoforms and that they are UV sensitive. Sensitivity of CC cells required dTRPA1 and H 2 O 2 production but not conventional phototransduction molecules. Our results suggest that specific isoforms of dTRPA1 can sense UV light via photochemical production of H 2 O 2 . We speculate that UV sensitivity conferred by these isoforms in CC cells may allow young larvae to activate stress response-a function of CC cells-when they encounter strong UV, an aversive stimulus for young larvae.UV sensing | dTRPA1 isoforms | reactive oxygen species | Drosophila | optogenetics

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