Somers Jason, Luong Hang Ngoc Bao, Mitchell Judith, Batterham Philip, Perry Trent
School of BioSciences, University of Melbourne, Victoria 3010, Australia.
Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia.
Genetics. 2017 Jan;205(1):263-271. doi: 10.1534/genetics.116.195750. Epub 2016 Nov 9.
Nicotinic acetylcholine receptors (nAChRs) are a highly conserved gene family that form pentameric receptors involved in fast excitatory synaptic neurotransmission. The specific roles individual nAChR subunits perform in Drosophila melanogaster and other insects are relatively uncharacterized. Of the 10 D. melanogaster nAChR subunits, only three have described roles in behavioral pathways; Dα3 and Dα4 in sleep, and Dα7 in the escape response. Other subunits have been associated with resistance to several classes of insecticides. In particular, our previous work has demonstrated that an allele of the Dα1 subunit is associated with resistance to neonicotinoid insecticides. We used ends-out gene targeting to create a knockout of the Dα1 gene to facilitate phenotypic analysis in a controlled genetic background. To our knowledge, this is the first report of a native function for any nAChR subunits known to be targeted by insecticides. Loss of Dα1 function was associated with changes in courtship, sleep, longevity, and insecticide resistance. While acetylcholine signaling had previously been linked with mating behavior and reproduction in D. melanogaster, no specific nAChR subunit had been directly implicated. The role of Dα1 in a number of behavioral phenotypes highlights the importance of understanding the biological roles of nAChRs and points to the fitness cost that may be associated with neonicotinoid resistance.
烟碱型乙酰胆碱受体（nAChRs）是一个高度保守的基因家族，它们形成五聚体受体，参与快速兴奋性突触神经传递。单个nAChR亚基在黑腹果蝇和其他昆虫中所起的具体作用相对还不清楚。在黑腹果蝇的10个nAChR亚基中，只有3个在行为途径中所起的作用有描述；Dα3和Dα4与睡眠有关，Dα7与逃避反应有关。其他亚基与对几类杀虫剂的抗性有关。特别是，我们之前的研究表明，Dα1亚基的一个等位基因与对新烟碱类杀虫剂的抗性有关。我们使用末端外显子基因靶向技术创建了Dα1基因的敲除品系，以便在可控的遗传背景下进行表型分析。据我们所知，这是已知被杀虫剂靶向的任何nAChR亚基的天然功能的首次报道。Dα1功能的丧失与求偶、睡眠、寿命和杀虫剂抗性的变化有关。虽然乙酰胆碱信号传导此前已与黑腹果蝇的交配行为和繁殖联系在一起，但没有特定的nAChR亚基被直接牵连。Dα1在多种行为表型中的作用突出了理解nAChRs生物学作用的重要性，并指出了可能与新烟碱类抗性相关的适应性代价。
