Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol.

Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol.
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DOI:
10.3390/ijms222010997
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发表时间:
2021-10-12
影响因子:
5.6
通讯作者:
Talavera K
Talavera K
中科院分区:
生物学2区
文献类型:
--
作者:
Boonen B;Startek JB;Milici A;López-Requena A;Beelen M;Callaerts P;Talavera K

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背景:瞬态受体电位锚蛋白1 (TRPA1)阳离子通道在许多物种中起着广泛调谐的有害化学物质传感器的作用。最近的研究在果蝇中发现了四种功能性TRPA1亚型(dTRPA1(A)至(D)),但它们对非亲电性化学物质的反应尚未得到充分表征。方法:我们确定了成年果蝇对哺乳动物TRPA1非亲电激活剂香橼醛和薄荷醇的行为反应,并利用细胞内Ca2+成像和全细胞膜片钳记录表征了这些化合物对所有四种dTRPA1通道异构体的影响。结果:野生型果蝇在嗅觉测试中避免了香茅和薄荷醇,而dTrpA1突变果蝇的这种行为减少了。这两种化合物在HEK293T异源表达系统中激活所有dTRPA1异构体,其敏感性序列如下:dTRPA1(C) = dTRPA1(D) > dTRPA1(A)比dTRPA1(B), dTRPA1(A) > dTRPA1(D) > dTRPA1(C) > dTRPA1(B)对薄荷醇。结论:黑胃果蝇对香茅醛和薄荷醇的正常回避需要dTrpA1。所有的dTRPA1亚型都被这两种化合物激活,但dTRPA1(B)始终是最不敏感的。我们讨论了这些发现如何指导进一步研究TRPA1通道的生理作用和化学敏感性的结构基础。
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 Drosophila melanogaster (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 Ca2+ 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 dTrpA1 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: dTrpA1 was required for the normal avoidance of Drosophila melanogaster 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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