A natural polymorphism alters odour and DEET sensitivity in an insect odorant receptor.
A natural polymorphism alters odour and DEET sensitivity in an insect odorant receptor.
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DOI：
10.1038/nature10438
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发表时间：
2011-09-21
期刊：
影响因子：
64.8
通讯作者：
Vosshall, Leslie B.
中科院分区：
文献类型：
--
作者：
Pellegrino, Maurizio;Steinbach, Nicole;Stensmyr, Marcus C.;Hansson, Bill S.;Vosshall, Leslie B.
蚊子等食血昆虫是人类传染病的有效媒介，因为它们被体热、二氧化碳和脊椎动物宿主产生的气味强烈吸引。含有DEET(N，N-二乙基-间甲苯胺)的驱虫剂是非常有效的，但这种化学物质防止叮咬昆虫的机制尽管进行了数十年的研究，但仍存在争议。DEET似乎既在近距离作用于昆虫的味觉受体，又在远距离作用于嗅觉系统，作为接触性化学物质发挥作用。对于DEET在气相中观察到的行为影响，已经提出了两种相反的机制：DEET干扰嗅觉系统以阻止宿主气味识别，或者DEET通过激活引起回避行为的嗅神经元来主动驱赶昆虫。在这里，我们表明，驱虫剂DEET的功能是由昆虫气味受体(OR)复合体形成的气味门控离子通道的调制器。昆虫的功能OR复合体由一个共同的共受体Orco(参考文献)组成。，以前称为Or83b，参考文献)，以及一个或多个赋予气味选择性的可变OR亚基。DEET作用于该复合体以增强或抑制气味诱发的活性或抑制气味诱发的自发活动。这种调节依赖于特定的OR以及气味配体的浓度和特性。我们在来自巴西的果蝇黑腹果蝇品系中发现了Or59b第二跨膜结构域的单一氨基酸多态性，使该受体对气味配体的抑制和DEET的调节不敏感。这些数据提供了第一个证据，表明自然变异可以改变特定气味昆虫或对气味配体和DEET的敏感性。我们的数据支持这样的假设，即DEET充当了一个分子“混乱剂”，扰乱了昆虫气味密码，并为DEET对多种昆虫物种的广谱疗效提供了一个令人信服的解释。
Blood-feeding insects such as mosquitoes are efficient vectors of human infectious diseases because they are strongly attracted by body heat, carbon dioxide, and odours produced by their vertebrate hosts. Insect repellents containing DEET (N,N-diethyl-meta-toluamide) are highly effective, but the mechanism by which this chemical wards off biting insects remains controversial despite decades of investigation. DEET appears to act both at close range as a contact chemorepellent by acting on insect gustatory receptors and at long range by acting on the olfactory system. Two opposing mechanisms for the observed behavioural effects of DEET in the gas phase have been proposed: that DEET interferes with the olfactory system to block host odour recognition or that DEET actively repels insects by activating olfactory neurons that elicit avoidance behaviour. Here we show that the insect repellent DEET functions as a modulator of the odour-gated ion channel formed by the insect odorant receptor (OR) complex. The functional insect OR complex consists of a common co-receptor, Orco (ref. , formerly called Or83b, ref), and one or more variable OR subunits that confer odour-selectivity. DEET acts on this complex to potentiate or inhibit odour-evoked activity or to inhibit odour-evoked suppression of spontaneous activity. This modulation depends on the specific OR and the concentration and identity of the odour ligand. We identify a single amino acid polymorphism in the second transmembrane domain of Or59b in a Drosophila melanogaster strain from Brazil that renders this receptor insensitive to inhibition by the odour ligand and modulation by DEET. These data provide the first evidence that natural variation can modify the sensitivity of an odour-specific insect OR to odour ligands and DEET. Our data support the hypothesis that DEET acts as a molecular “confusant” that scrambles the insect odour code and provide a compelling explanation for the broad-spectrum efficacy of DEET against multiple insect species.
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影响因子：
16.2
作者：
Lee, Youngseok;Kim, Sang Hoon;Montell, Craig
通讯作者：
Montell, Craig
影响因子：
2.2
作者：
Reeder, NL;Ganz, PJ;Saunders, CW
通讯作者：
Saunders, CW
DOI：
10.1073/pnas.1001313107
发表时间：
2010-05-11
影响因子：
11.1
作者：
Stanczyk, Nina M.;Brookfield, John F. Y.;Field, Linda M.
通讯作者：
Field, Linda M.
影响因子：
2.1
作者：
Dogan, EB;Rossignol, PA
通讯作者：
Rossignol, PA
影响因子：
16.2
作者：
Dobritsa, AA;van der Goes van Naters, W;Carlson, JR
通讯作者：
Carlson, JR