Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol

• Published in: International journal of molecular sciences 2021-10, Vol.22 (20), p.10997
• Main Authors: Boonen, Brett, Startek, Justyna B, Milici, Alina, López-Requena, Alejandro, Beelen, Melissa, Callaerts, Patrick, Talavera, Karel
• Format: Article
• Language: English
• Subjects: Acyclic Monoterpenes - pharmacology; Aldehydes - pharmacology; Animals; Animals, Genetically Modified - metabolism; Calcium (intracellular); Calcium - metabolism; Calcium imaging; Calcium ions; Citronellal; Drosophila melanogaster; Drosophila melanogaster - drug effects; Drosophila melanogaster - metabolism; Drosophila Proteins - deficiency; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Female; Fruit flies; HEK293 Cells; Humans; Insect Repellents - pharmacology; Insects; Isoforms; Male; Mammals; Menthol; Menthol - pharmacology; Patch-Clamp Techniques; Protein Isoforms - deficiency; Protein Isoforms - genetics; Protein Isoforms - metabolism; Sensitivity; Transient receptor potential proteins; TRPA1 Cation Channel - deficiency; TRPA1 Cation Channel - genetics; TRPA1 Cation Channel - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222010997

The transient receptor potential ankyrin 1 (TRPA1) cation channels function as broadly-tuned sensors of noxious chemicals in many species. Recent studies identified four functional TRPA1 isoforms in (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be fully characterized. We determined the behavioral responses of adult flies to the mammalian TRPA1 non-electrophilic activators citronellal and menthol, and characterized the effects of these compounds on all four dTRPA1 channel isoforms using intracellular Ca imaging and whole-cell patch-clamp recordings. Wild type flies avoided citronellal and menthol in an olfactory test and this behavior was reduced in mutant flies. Both compounds activate all dTRPA1 isoforms in the heterologous expression system HEK293T, with the following sensitivity series: dTRPA1(C) = dTRPA1(D) > dTRPA1(A) ≫ dTRPA1(B) for citronellal and dTRPA1(A) > dTRPA1(D) > dTRPA1(C) > dTRPA1(B) for menthol. was required for the normal avoidance of towards citronellal and menthol. All dTRPA1 isoforms are activated by both compounds, but the dTRPA1(B) is consistently the least sensitive. We discuss how these findings may guide further studies on the physiological roles and the structural bases of chemical sensitivity of TRPA1 channels.