Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception.
Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception.
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作者：
化学伤害感受，检测组织损伤化学物质，对动物生存很重要，并导致人类疼痛和炎症，但其进化起源在很大程度上是未知的。反应性亲电体是一类人类认为辛辣刺激的有毒化合物，如异硫氰酸烯丙酯（芥末中）和丙烯醛（香烟烟雾中）。昆虫对人类来说，反应性亲电体是令人厌恶的，但这是否反映了一种古老的感觉方式的保护尚不清楚。在这里，我们确定了果蝇中反应性亲电检测的分子基础。我们证明，dTRPA1，果蝇的人类刺激性传感器的直系同源物，在味觉化学传感器，以抑制反应性亲电体摄入。我们表明，苍蝇和蚊子的TRPA1直系同源物是亲电体的分子传感器，使用与脊椎动物TRPA1s保守的机制。系统发育分析表明，无脊椎动物和脊椎动物TRPA1共享一个共同的祖先，拥有亲电检测所需的关键特征。这些发现支持出现TRPA1为基础的亲电检测在一个共同的两侧祖先，在整个脊椎动物和无脊椎动物进化的广泛保护。这种保守性与典型嗅觉和味觉受体的进化分歧形成对比，可能与亲电毒性有关。我们提出人类的疼痛感知依赖于一种古老的化学传感器，这种传感器在大约5亿年的动物进化中保存下来。
Chemical nociception, the detection of tissue-damaging chemicals, is important for animal survival and causes human pain and inflammation, but its evolutionary origins are largely unknown. Reactive electrophiles are a class of noxious compounds humans find pungent and irritating, like allyl isothiocyanate (in wasabi) and acrolein (in cigarette smoke). Insects to humans find reactive electrophiles aversive, but whether this reflects conservation of an ancient sensory modality has been unclear. Here we identify the molecular basis of reactive electrophile detection in flies. We demonstrate that dTRPA1, the Drosophila melanogaster ortholog of the human irritant sensor, acts in gustatory chemosensors to inhibit reactive electrophile ingestion. We show that fly and mosquito TRPA1 orthologs are molecular sensors of electrophiles, using a mechanism conserved with vertebrate TRPA1s. Phylogenetic analyses indicate invertebrate and vertebrate TRPA1s share a common ancestor that possessed critical characteristics required for electrophile detection. These findings support emergence of TRPA1-based electrophile detection in a common bilaterian ancestor, with widespread conservation throughout vertebrate and invertebrate evolution. Such conservation contrasts with the evolutionary divergence of canonical olfactory and gustatory receptors and may relate to electrophile toxicity. We propose human pain perception relies on an ancient chemical sensor conserved across ~500 million years of animal evolution.
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影响因子：
9.2
作者：
Al-Anzi, Bader;Tracey, W. Daniel, Jr.;Benzer, Seymour
通讯作者：
Benzer, Seymour
影响因子：
16.2
作者：
Kwan, KY;Allchorne, AJ;Corey, DP
通讯作者：
Corey, DP
影响因子：
5.3
作者：
Sokabe, Takaaki;Tsujiuchi, Seiya;Tominaga, Makoto
通讯作者：
Tominaga, Makoto
DOI：
10.1152/physiol.00026.2008
发表时间：
2008-12
期刊：
Physiology (Bethesda, Md.)
影响因子：
--
作者：
Bessac BF;Jordt SE
通讯作者：
Jordt SE
影响因子：
2.5
作者：
Pulver, Stefan R.;Pashkovski, Stanislav L.;Griffith, Leslie C.
通讯作者：
Griffith, Leslie C.