Jones Andrew K, Raymond-Delpech Valerie, Thany Steeve H, Gauthier Monique, Sattelle David B
MRC Functional Genetics Unit, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom.
Genome Res. 2006 Nov;16(11):1422-30. doi: 10.1101/gr.4549206. Epub 2006 Oct 25.
Nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic synaptic transmission and play roles in many cognitive processes. They are under intense research as potential targets of drugs used to treat neurodegenerative diseases and neurological disorders such as Alzheimer's disease and schizophrenia. Invertebrate nAChRs are targets of anthelmintics as well as a major group of insecticides, the neonicotinoids. The honey bee, Apis mellifera, is one of the most beneficial insects worldwide, playing an important role in crop pollination, and is also a valuable model system for studies on social interaction, sensory processing, learning, and memory. We have used the A. mellifera genome information to characterize the complete honey bee nAChR gene family. Comparison with the fruit fly Drosophila melanogaster and the malaria mosquito Anopheles gambiae shows that the honey bee possesses the largest family of insect nAChR subunits to date (11 members). As with Drosophila and Anopheles, alternative splicing of conserved exons increases receptor diversity. Also, we show that in one honey bee nAChR subunit, six adenosine residues are targeted for RNA A-to-I editing, two of which are evolutionarily conserved in Drosophila melanogaster and Heliothis virescens orthologs, and that the extent of editing increases as the honey bee lifecycle progresses, serving to maximize receptor diversity at the adult stage. These findings on Apis mellifera enhance our understanding of nAChR functional genomics and provide a useful basis for the development of improved insecticides that spare a major beneficial insect species.
烟碱型乙酰胆碱受体(nAChRs)介导快速胆碱能突触传递,并在许多认知过程中发挥作用。作为治疗神经退行性疾病和神经紊乱(如阿尔茨海默病和精神分裂症)药物的潜在靶点,它们正受到深入研究。无脊椎动物的nAChRs是驱虫药以及一大类杀虫剂(新烟碱类)的作用靶点。蜜蜂(Apis mellifera)是全球最有益的昆虫之一,在作物授粉中发挥着重要作用,也是研究社会互动、感觉加工、学习和记忆的宝贵模型系统。我们利用蜜蜂基因组信息对完整的蜜蜂nAChR基因家族进行了表征。与果蝇(Drosophila melanogaster)和疟蚊(Anopheles gambiae)的比较表明,蜜蜂拥有迄今为止最大的昆虫nAChR亚基家族(11个成员)。与果蝇和疟蚊一样,保守外显子的可变剪接增加了受体的多样性。此外,我们还表明,在一个蜜蜂nAChR亚基中,六个腺苷残基被靶向进行RNA A到I编辑,其中两个在黑腹果蝇和烟芽夜蛾的直系同源物中是进化保守的,并且随着蜜蜂生命周期的推进,编辑程度增加,有助于在成年阶段最大化受体多样性。这些关于蜜蜂的发现增进了我们对nAChR功能基因组学的理解,并为开发对一种主要有益昆虫物种无害的改良杀虫剂提供了有用的基础。