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Cofactor-enabled functional expression of fruit fly, honeybee, and bumblebee nicotinic receptors reveals picomolar neonicotinoid actions.
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2020-07-14 , DOI: 10.1073/pnas.2003667117
Makoto Ihara 1 , Shogo Furutani 1 , Sho Shigetou 1 , Shota Shimada 1 , Kunihiro Niki 1 , Yuma Komori 1 , Masaki Kamiya 1 , Wataru Koizumi 1 , Leo Magara 1 , Mai Hikida 1 , Akira Noguchi 1 , Daiki Okuhara 1 , Yuto Yoshinari 2 , Shu Kondo 3 , Hiromu Tanimoto 4 , Ryusuke Niwa 5 , David B Sattelle 6 , Kazuhiko Matsuda 7, 8
Affiliation  

The difficulty of achieving robust functional expression of insect nicotinic acetylcholine receptors (nAChRs) has hampered our understanding of these important molecular targets of globally deployed neonicotinoid insecticides at a time when concerns have grown regarding the toxicity of this chemotype to insect pollinators. We show that thioredoxin-related transmembrane protein 3 (TMX3) is essential to enable robust expression in Xenopus laevis oocytes of honeybee (Apis mellifera) and bumblebee (Bombus terrestris) as well as fruit fly (Drosophila melanogaster) nAChR heteromers targeted by neonicotinoids and not hitherto robustly expressed. This has enabled the characterization of picomolar target site actions of neonicotinoids, findings important in understanding their toxicity.



中文翻译:

果蝇,蜜蜂和大黄蜂烟碱样受体的辅因子激活功能性表达揭示了皮摩尔的新烟碱作用。

昆虫烟碱型乙酰胆碱受体(nAChRs)的功能表达难以实现,这使我们对这种化学型对昆虫授粉媒介的毒性产生担忧的时候,阻碍了我们对全球部署的新烟碱类杀虫剂这些重要分子靶标的理解。我们显示,与硫氧还蛋白有关的跨膜蛋白3(TMX3)对使蜜蜂(Apis mellifera)和大黄蜂(Bombus terrestris)以及果蝇Drosophila melanogaster)的非洲爪蟾卵母细胞中能够稳定表达至关重要)新烟碱类靶向的nAChR异聚体,迄今尚未得到强有力的表达。这使得能够表征新烟碱的皮摩尔目标部位的作用,这一发现对于理解其毒性很重要。

更新日期:2020-07-14
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