Convergent evolution of noxious heat sensing by TRPA5, a novel class of heat sensor in Rhodnius prolixus

Insects are ectotherms, and as such, rely on a diverse repertoire of thermoreceptors to monitor environmental temperature and control behavioral thermoregulation. Here, we use structural, phylogenetic, genetic, and functional analyses to show that TRPA5 genes, widespread across numerous insect orders, encode a novel class of noxious heat receptors. We show that in the triatomine bug Rhodnius prolixus, the primary vector of Chagas disease, Rp-TRPA52 differs biophysically and structurally from noxious thermoTRPAs previously described in insects. This includes key changes in the ankyrin repeat domain and the selectivity filter of the channel. In vitro, we find evidence that the homo-tetrameric channel is not activated by voltage, but displays high thermosensitivity with an enthalpy change (ΔH) of 72 kcal/mol associated with the channel activation, with a Q10 = 25 and T°half = 58.6°C. Structural analyses reveal parallels in the overall ion channel architecture between fruit fly TRPA1 and Rp-TRPA52; however, functional properties and expression patterns indicate that the role of Rp-TRPA52 is more similar to that of Pyrexia noxious heat receptors found in fruit flies. Pyrexia genes have been lost in true bugs, and our findings suggest that the rapidly evolving insect TRPA gene family has given rise to an independent evolutionary origin of a molecular transducer that is responsive to noxious thermal stimuli.