Nucleophile sensitivity of Drosophila TRPA1 underlies light-induced feeding deterrence
Nucleophile sensitivity of Drosophila TRPA1 underlies light-induced feeding deterrence
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DOI：
10.7554/elife.18425
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发表时间：
2016-09-22
期刊：
影响因子：
7.7
通讯作者：
Kang, KyeongJin
中科院分区：
文献类型：
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作者：
Du, Eun Jo;Ahn, Tae Jung;Kang, KyeongJin
包括紫外线 (UV) 在内的太阳辐射会产生反应性自由基，从而导致组织损伤，自由基由于不成对电子而可能具有亲电子或亲核性。关于动物如何快速检测和避免自然阳光诱导的自由基，人们知之甚少。我们发现果蝇瞬时受体电位锚蛋白 1 (TRPA1) 以前仅被称为亲电子受体，可通过亲核试剂敏感性灵敏地检测光化学活性阳光。尽管 TRPA1(A) 和 TRPA1(B) 亚型具有相似的亲电子敏感性，但果蝇中的快速光依赖性摄食威慑仅由 TRPA1(A) 亚型介导。这种异构体依赖性在结构变化的亲核化合物和亲核性伴随的过氧化氢 (H2O2) 的检测中再次出现。此外，这些异构体依赖性机制需要一组通用的 TRPA1(A) 特异性残基，对于亲电试剂检测来说是可有可无的。总的来说，TRPA1(A) 通过其作为光化学产生的自由基受体的亲核敏感性，对自然阳光强度做出快速反应，导致果蝇发生急性光诱导行为转变。
Solar irradiation including ultraviolet (UV) light causes tissue damage by generating reactive free radicals that can be electrophilic or nucleophilic due to unpaired electrons. Little is known about how free radicals induced by natural sunlight are rapidly detected and avoided by animals. We discover that Drosophila Transient Receptor Potential Ankyrin 1 (TRPA1), previously known only as an electrophile receptor, sensitively detects photochemically active sunlight through nucleophile sensitivity. Rapid light-dependent feeding deterrence in Drosophila was mediated only by the TRPA1(A) isoform, despite the TRPA1(A) and TRPA1(B) isoforms having similar electrophile sensitivities. Such isoform dependence re-emerges in the detection of structurally varied nucleophilic compounds and nucleophilicity-accompanying hydrogen peroxide (H2O2). Furthermore, these isoform-dependent mechanisms require a common set of TRPA1(A)-specific residues dispensable for electrophile detection. Collectively, TRPA1(A) rapidly responds to natural sunlight intensities through its nucleophile sensitivity as a receptor of photochemically generated radicals, leading to an acute light-induced behavioral shift in Drosophila.