Activation of <i>Drosophila melanogaster</i> TRPA1 Isoforms by Citronellal and Menthol
Background: 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 <i>Drosophila melanogaster</i> (dTRPA1(A) to (D)), but their responses to non...
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/20/10997 |
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| author | Brett Boonen Justyna B. Startek Alina Milici Alejandro López-Requena Melissa Beelen Patrick Callaerts Karel Talavera |
| author_facet | Brett Boonen Justyna B. Startek Alina Milici Alejandro López-Requena Melissa Beelen Patrick Callaerts Karel Talavera |
| author_sort | Brett Boonen |
| collection | DOAJ |
| description | Background: 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 <i>Drosophila melanogaster</i> (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be fully characterized. Methods: 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<sup>2+</sup> imaging and whole-cell patch-clamp recordings. Results: Wild type flies avoided citronellal and menthol in an olfactory test and this behavior was reduced in <i>dTrpA1</i> 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. Conclusions: <i>dTrpA1</i> was required for the normal avoidance of <i>Drosophila melanogaster</i> 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. |
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| last_indexed | 2024-03-10T06:30:45Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-614e9f4f0d81497f9037a40634424d892023-11-22T18:32:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122201099710.3390/ijms222010997Activation of <i>Drosophila melanogaster</i> TRPA1 Isoforms by Citronellal and MentholBrett Boonen0Justyna B. Startek1Alina Milici2Alejandro López-Requena3Melissa Beelen4Patrick Callaerts5Karel Talavera6Leuven Center for Brain & Disease Research, Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB-KU 3000 Leuven, BelgiumLeuven Center for Brain & Disease Research, Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB-KU 3000 Leuven, BelgiumLeuven Center for Brain & Disease Research, Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB-KU 3000 Leuven, BelgiumLeuven Center for Brain & Disease Research, Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB-KU 3000 Leuven, BelgiumLaboratory of Behavioral and Developmental Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, BelgiumLaboratory of Behavioral and Developmental Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, BelgiumLeuven Center for Brain & Disease Research, Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB-KU 3000 Leuven, BelgiumBackground: 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 <i>Drosophila melanogaster</i> (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be fully characterized. Methods: 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<sup>2+</sup> imaging and whole-cell patch-clamp recordings. Results: Wild type flies avoided citronellal and menthol in an olfactory test and this behavior was reduced in <i>dTrpA1</i> 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. Conclusions: <i>dTrpA1</i> was required for the normal avoidance of <i>Drosophila melanogaster</i> 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.https://www.mdpi.com/1422-0067/22/20/10997TRPA1<i>Drosophila melanogaster</i>isoformcitronellalmentholAITC |
| spellingShingle | Brett Boonen Justyna B. Startek Alina Milici Alejandro López-Requena Melissa Beelen Patrick Callaerts Karel Talavera Activation of <i>Drosophila melanogaster</i> TRPA1 Isoforms by Citronellal and Menthol International Journal of Molecular Sciences TRPA1 <i>Drosophila melanogaster</i> isoform citronellal menthol AITC |
| title | Activation of <i>Drosophila melanogaster</i> TRPA1 Isoforms by Citronellal and Menthol |
| title_full | Activation of <i>Drosophila melanogaster</i> TRPA1 Isoforms by Citronellal and Menthol |
| title_fullStr | Activation of <i>Drosophila melanogaster</i> TRPA1 Isoforms by Citronellal and Menthol |
| title_full_unstemmed | Activation of <i>Drosophila melanogaster</i> TRPA1 Isoforms by Citronellal and Menthol |
| title_short | Activation of <i>Drosophila melanogaster</i> TRPA1 Isoforms by Citronellal and Menthol |
| title_sort | activation of i drosophila melanogaster i trpa1 isoforms by citronellal and menthol |
| topic | TRPA1 <i>Drosophila melanogaster</i> isoform citronellal menthol AITC |
| url | https://www.mdpi.com/1422-0067/22/20/10997 |
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