Organic anion-transporting polypeptides are involved in the elimination of insecticides from the red flour beetle, Tribolium castaneum

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. [GRAPHICS] .