Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels
Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels
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DOI：
10.1038/nature06861
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发表时间：
2008-04-24
期刊：
影响因子：
64.8
通讯作者：
Hansson, Bill S.
中科院分区：
文献类型：
--
作者：
Wicher, Dieter;Schaefer, Ronny;Hansson, Bill S.
从蠕虫到人类，许多气味信号是通过挥发性配体与气味受体（1）的结合来感知的，气味受体属于G蛋白偶联受体（GPCR）家族（2）。它们与异源三聚体G蛋白偶联，其中大多数诱导cAMP产生（3）。然后，该第二信使激活环核苷酸门控离子通道以使嗅觉受体神经元去兴奋，从而为进一步的神经元加工提供信号。然而，最近的发现挑战了昆虫中气味信号转导的这一概念，因为它们的气味受体与其他GPCR缺乏任何序列相似性（4），由常规气味受体（例如，Or22a）组成，与普遍表达的伴侣蛋白（5），如果蝇中的Or83b（6）二聚化。Or83b具有类似于GPCR的结构，但在质膜中具有相反的取向（4，7）。然而，G蛋白在昆虫嗅觉受体神经元中表达（8），并且嗅觉感知通过影响cAMP转导途径的突变而改变（9）。在这里，我们表明，应用气味共表达Or22a和Or83b的哺乳动物细胞的结果在非选择性阳离子电流激活的离子和代谢途径的装置，和随后的细胞内Ca2+浓度的增加。Or83b单独表达导致功能性离子通道不直接响应气味剂，而是直接被细胞内cAMP或cGMP激活。昆虫气味受体因此形成配体门控通道以及气味感受单元和环核苷酸激活的非选择性阳离子通道的复合物。因此，它们提供快速和瞬时以及敏感和延长的气味信号传导。
From worm to man, many odorant signals are perceived by the binding of volatile ligands to odorant receptors(1) that belong to the G- protein- coupled receptor ( GPCR) family(2). They couple to heterotrimeric G- proteins, most of which induce cAMP production(3). This second messenger then activates cyclic- nucleotide-gated ion channels to depolarize the olfactory receptor neuron, thus providing a signal for further neuronal processing. Recent findings, however, have challenged this concept of odorant signal transduction in insects, because their odorant receptors, which lack any sequence similarity to other GPCRs(4), are composed of conventional odorant receptors ( for example, Or22a), dimerized with a ubiquitously expressed chaperone protein(5), such as Or83b in Drosophila(6). Or83b has a structure akin to GPCRs, but has an inverted orientation in the plasma membrane(4,7). However, G proteins are expressed in insect olfactory receptor neurons(8), and olfactory perception is modified by mutations affecting the cAMP transduction pathway(9). Here we show that application of odorants to mammalian cells co- expressing Or22a and Or83b results in non- selective cation currents activated by means of an ionotropic and a metabotropic pathway, and a subsequent increase in the intracellular Ca2+ concentration. Expression of Or83b alone leads to functional ion channels not directly responding to odorants, but being directly activated by intracellular cAMP or cGMP. Insect odorant receptors thus form ligand- gated channels as well as complexes of odorant- sensing units and cyclic- nucleotide- activated non- selective cation channels. Thereby, they provide rapid and transient as well as sensitive and prolonged odorant signalling.