PMID- 36087889 OWN - NLM STAT- MEDLINE DCOM- 20221011 LR - 20221027 IS - 1879-0240 (Electronic) IS - 0965-1748 (Linking) VI - 149 DP - 2022 Oct TI - TRPV channel nanchung and TRPA channel water witch form insecticide-activated complexes. PG - 103835 LID - S0965-1748(22)00117-5 [pii] LID - 10.1016/j.ibmb.2022.103835 [doi] AB - We have previously shown that insect vanilloid-type transient receptor potential (TRPV) channels Nanchung (Nan) and Inactive (Iav) form complexes, which can be over-stimulated and eventually silenced by commercial insecticides, afidopyropen, pymetrozine and pyrifluquinazon. Silencing of the TRPV channels by the insecticides perturbs function of the mechano-sensory organs, chordotonal organs, disrupting sound perception, gravitaxis, and feeding. In addition to TRPV channels, chordotonal organs express an ankyrin-type transient receptor potential (TRPA) channel, Water witch (Wtrw). Genetic data implicate Wtrw in sound and humidity sensing, although the signaling pathway, which links Wtrw to these functions has not been clearly defined. Here we show that, in heterologous system, Nan and Wtrw form calcium channels, which can be activated by afidopyropen, pymetrozine and an endogenous agonist, nicotinamide. Analogous to Nan-Iav heteromers, Nan forms the main binding interface for afidopyropen, whereas co-expression of Wtrw dramatically increases its binding affinity. Pymetrozine competes with afidopyropen for binding to Nan-Wtrw complexes, suggesting that these compounds have overlapping binding sites. Analysis of Drosophila single-nucleus transcriptomic atlas revealed co-expression of nan and wtrw in audio- and mechanosensory neurons. The observation that Nan can form insecticide-sensitive heteromers with more than one type of TRP channels, raises a possibility that Nan may partner with some other TRP channel(s). In addition, we show that Wtrw can be activated by plant-derived reactive electrophiles, allyl isothiocyanate and cinnamaldehyde, defining new molecular target for these repellents. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Kandasamy, Ramani AU - Kandasamy R AD - BASF Corporation, 26 Davis Drive, Research Triangle Park, NC, 27709, USA. FAU - Costea, Paul Igor AU - Costea PI AD - BASF SE, RGD/BE, Carl-Bosch-Strasse 38, 67056, Ludwigshafen am Rhein, Germany. FAU - Stam, Lynn AU - Stam L AD - BASF Corporation, 26 Davis Drive, Research Triangle Park, NC, 27709, USA. FAU - Nesterov, Alexandre AU - Nesterov A AD - BASF Corporation, 26 Davis Drive, Research Triangle Park, NC, 27709, USA. Electronic address: alexandre.nesterov@basf.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220907 PL - England TA - Insect Biochem Mol Biol JT - Insect biochemistry and molecular biology JID - 9207282 RN - 0 (Ankyrins) RN - 0 (Aquaporins) RN - 0 (Calcium Channels) RN - 0 (Heterocyclic Compounds, 4 or More Rings) RN - 0 (Insecticides) RN - 0 (Lactones) RN - 0 (Transient Receptor Potential Channels) RN - 0 (afidopyropen) RN - 059QF0KO0R (Water) RN - 25X51I8RD4 (Niacinamide) SB - IM MH - Animals MH - Ankyrins/metabolism MH - *Aquaporins MH - Calcium Channels/genetics MH - Drosophila/metabolism MH - Heterocyclic Compounds, 4 or More Rings MH - *Insecticides/pharmacology MH - Lactones MH - Niacinamide MH - *Transient Receptor Potential Channels/genetics MH - Water/metabolism OTO - NOTNLM OT - Insecticides OT - Nanchung OT - Repellents OT - TRPA channels OT - TRPV channels OT - Water witch COIS- Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript. EDAT- 2022/09/11 06:00 MHDA- 2022/10/12 06:00 CRDT- 2022/09/10 19:36 PHST- 2022/05/25 00:00 [received] PHST- 2022/08/23 00:00 [revised] PHST- 2022/09/02 00:00 [accepted] PHST- 2022/09/11 06:00 [pubmed] PHST- 2022/10/12 06:00 [medline] PHST- 2022/09/10 19:36 [entrez] AID - S0965-1748(22)00117-5 [pii] AID - 10.1016/j.ibmb.2022.103835 [doi] PST - ppublish SO - Insect Biochem Mol Biol. 2022 Oct;149:103835. doi: 10.1016/j.ibmb.2022.103835. Epub 2022 Sep 7.