Abstract

Organic anion-transporting polypeptides (OATPs) are integral membrane transporters that mediate cellular uptake of a broad range of substrates in humans. The functions of OATPs in insects are less well investigated and only poorly understood. A large number of compounds potentially toxic to insects are organic anions that include secondary plant and insecticide-derived metabolites. Some insect OATP genes are expressed in metabolic, neuroprotective and excreting tissues, and they are co-expressed together with genes known to be involved in detoxification and excretion. Therefore, a role in the elimination of insecticides has been proposed for OATPs, but experimental proof was pending. The aim of this study was to identify OATPs that affect tolerance to insecticides in the red flour beetle, Tribolium castaneum, a genomic model species and stored product pest. We determined expression profiles of TcOATP genes in different tissues and developmental stages and analyzed RNAi phenotypes. We found that some TcOATP genes had particularly high transcript levels in relevant tissues and that knockdown of TcOATP4-C1 led to sever developmental defects during larval–pupal molt. Then, we exposed the larvae to different chemically unrelated insecticides and analyzed transcript levels and mortalities. Some genes were specifically upregulated in response to insecticide treatment, and mortalities observed after administering certain insecticides were significantly increased when specific TcOATPs were silenced. By applying systemic RNAi in T. castaneum, we provide first evidence that OATPs are involved in the elimination of insecticides and hence may contribute to insecticide resistance, which becomes an increasingly serious problem in agriculture and forestry.

Graphic abstract

中文翻译：

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有机阴离子运输多肽参与消除红面粉甲虫Tribolium castaneum中的杀虫剂

摘要

有机阴离子转运多肽（OATP）是不可或缺的膜转运蛋白，可介导人体对多种底物的细胞摄取。OATP在昆虫中的功能研究较少，只有很少了解。许多对昆虫有潜在毒性的化合物是有机阴离子，其中包括次生植物和杀虫剂衍生的代谢产物。一些昆虫的OATP基因在代谢，神经保护和排泄组织中表达，它们与已知与排毒和排泄有关的基因一起共表达。因此，已经提出了对于OATPs在消除杀虫剂中的作用，但是尚待实验证明。这项研究的目的是确定影响红粉甲虫对杀虫剂的耐受性的OATP，bol藜Tribolium castaneum是一种基因组模型物种，具有储藏的有害生物。我们确定了TcOATP基因在不同组织和发育阶段的表达谱，并分析了RNAi表型。我们发现某些TcOATP基因在相关组织中的转录水平特别高，而TcOATP4-C1的敲低导致幼虫－pu蜕皮中严重的发育缺陷。然后，我们将幼虫暴露于不同化学上不相关的杀虫剂，并分析转录本水平和死亡率。某些基因响应杀虫剂处理而特异上调，并且当特定的TcOATP时，施用某些杀虫剂后观察到的死亡率显着增加被沉默了。通过在T. castaneum中应用系统性RNAi ，我们提供了第一个证据，表明OATP参与了杀虫剂的消除，因此可能促进杀虫剂的抗性，这在农业和林业中已成为日益严重的问题。

图形摘要