Takebayashi Mayuka, Mori Sumito, Ito Ryo, Takayama Koichi, Ojima Hisanori, Takeuchi Miyu, Takahashi Hiyori, Yamamoto Niina, Egawa Runa, Kimura Yuki, Ihara Makoto, Sasaki Ken, Sattelle David B, Matsuda Kazuhiko
Department of Applied Biological Chemistry, Faculty of Agriculture, Kindai University, Nara, Japan.
Graduate School of Agriculture, Tamagawa University, Tokyo, Japan.
Pest Manag Sci. 2025 May;81(5):2671-2677. doi: 10.1002/ps.8371. Epub 2024 Aug 21.
A transmembrane thioredoxin (TMX3) enables the functional expression of insect nicotinic acetylcholine receptors (nAChRs) in Xenopus laevis oocytes, while co-factors RIC-3 and UNC-50 regulate the receptor expression level. RIC-3 (resistant to inhibitors of cholinesterase 3) has been shown to diversify by its differential mRNA splicing patterns. How such diversity influences neonicotinoid sensitivity of nAChRs of beneficial insect species remains poorly understood. We have identified a RIC-3 variant expressed most abundantly in the thoracic ganglia of honeybee (Apis mellifera) workers and investigated its effects on the functional expression and pharmacology of Amα1/Amα8/Amβ1 and Amα1/Amα2/Amα8/Amβ1 nAChRs expressed in X. laevis oocytes. The AmRIC-3 enhanced the response amplitude to the acetylcholine (ACh) of these A. mellifera nAChRs when its cRNA was injected into oocytes at low concentrations but suppressed the ACh response amplitude at high concentrations. Co-expression of the AmRIC-3 had a minimal impact on the affinity of ACh, but changed the efficacy of imidacloprid and clothianidin, suggesting that the presence and the level of RIC-3 expression can affect the nAChR responses to ACh and neonicotinoids, depending on nAChR subunit composition in honeybees. © 2024 Society of Chemical Industry.
一种跨膜硫氧还蛋白（TMX3）能使昆虫烟碱型乙酰胆碱受体（nAChRs）在非洲爪蟾卵母细胞中实现功能性表达，而辅助因子RIC-3和UNC-50则调节受体的表达水平。RIC-3（对胆碱酯酶抑制剂3有抗性）已被证明因其不同的mRNA剪接模式而具有多样性。这种多样性如何影响有益昆虫物种nAChRs对新烟碱类药物的敏感性仍知之甚少。我们鉴定出一种在蜜蜂（西方蜜蜂）工蜂胸神经节中表达最丰富的RIC-3变体，并研究了其对非洲爪蟾卵母细胞中表达的Amα1/Amα8/Amβ1和Amα1/Amα2/Amα8/Amβ1 nAChRs的功能表达和药理学的影响。当以低浓度将AmRIC-3的cRNA注射到卵母细胞中时，它增强了这些蜜蜂nAChRs对乙酰胆碱（ACh）的反应幅度，但在高浓度时抑制了ACh反应幅度。AmRIC-3的共表达对ACh的亲和力影响最小，但改变了吡虫啉和噻虫胺的效力，这表明RIC-3表达的存在和水平可影响nAChR对ACh和新烟碱类药物的反应，这取决于蜜蜂中nAChR亚基的组成。© 2024化学工业协会。
