Insect olfactory receptors are heteromeric ligand-gated ion channels
Insect olfactory receptors are heteromeric ligand-gated ion channels
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DOI：
10.1038/nature06850
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发表时间：
2008-04-24
期刊：
影响因子：
64.8
通讯作者：
Touhara, Kazushige
中科院分区：
文献类型：
--
作者：
Sato, Koji;Pellegrino, Maurizio;Touhara, Kazushige
在昆虫中，每个嗅觉感觉神经元表达嗅觉受体（OR）基因家族的一个至三个配体结合成员，沿着高度保守和广泛表达的Or 83 b共受体（1-9）。功能性昆虫OR由化学计量未知但包含至少一个可变气味剂结合亚基和一个恒定Or 83 b家族亚基的异聚复合物组成（10-16）。昆虫OR与脊椎动物中的G-蛋白偶联化学感受受体缺乏同源性（17），并且具有独特的七跨膜拓扑结构，氨基末端位于细胞内（10，18）。在这里，我们提供的证据表明，异聚昆虫OR包括一类新的配体激活的非选择性阳离子通道。表达家蚕、果蝇或蚊子异聚体OR复合物的异源细胞在气味剂刺激下表现出细胞外Ca 2+内流和阳离子非选择性离子电导。气味诱发的OR电流不依赖于已知的G蛋白偶联的第二信使通路.昆虫OR复合物的快速响应动力学和OR-亚基依赖的K+离子选择性支持OR和Or 83 b之间的复合物本身赋予通道活性的假设。气味门控通道的直接证据是通过从外向外膜片钳记录表达昆虫OR复合物的非洲爪蟾卵母细胞和HEK 293 T细胞膜获得的。由昆虫OR复合物形成的配体门控离子通道似乎是昆虫获得对嗅觉环境作出反应的独特策略的基础。
In insects, each olfactory sensory neuron expresses between one and three ligand- binding members of the olfactory receptor ( OR) gene family, along with the highly conserved and broadly expressed Or83b co-receptor(1-9). The functional insect OR consists of a heteromeric complex of unknown stoichiometry but comprising at least one variable odorant- binding subunit and one constant Or83b family subunit(10-16). Insect ORs lack homology to G- protein-coupled chemosensory receptors in vertebrates(17) and possess a distinct seven- transmembrane topology with the amino terminus located intracellularly(10,18). Here we provide evidence that heteromeric insect ORs comprise a new class of ligand- activated nonselective cation channels. Heterologous cells expressing silkmoth, fruitfly or mosquito heteromeric OR complexes showed extracellular Ca2+ influx and cation- non- selective ion conductance on stimulation with odorant. Odour- evoked OR currents are independent of known G- protein- coupled second messenger pathways. The fast response kinetics and OR- subunit- dependent K+ ion selectivity of the insect OR complex support the hypothesis that the complex between OR and Or83b itself confers channel activity. Direct evidence for odorant- gated channels was obtained by outside- out patch- clamp recording of Xenopus oocyte and HEK293T cell membranes expressing insect OR complexes. The ligand- gated ion channel formed by an insect OR complex seems to be the basis for a unique strategy that insects have acquired to respond to the olfactory environment.