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

Rösner, Janin; Tietmeyer, Johanne; Merzendorfer, Hans

doi:10.1007/s10340-020-01317-4

Cited by 9 publications

(12 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in line with DmOatp74D, which seems to be essential for the development of larval stages since homozygous mutant flies arrested at L1 stage, failing to molt to the second larval instar [24]. Our results are also consistent with a previous study in Tribolium castaneum, in which decreased larval survival and failure of pupation was observed upon silencing of TcOATP4-C1, a putative ortholog of the Drosophila Oatp74D [55]. Increased larval mortality was also observed in Aedes aegypti upon silencing of EcI-2 which induced 70-80% lethality [26].…”

Section: Oatp74d Is Essential For Lepidopteran Insect Development And...supporting

confidence: 92%

Functional characterization of putative ecdysone transporters in lepidopteran pests

Samantsidis

Fotiadou

Tzavellas

et al. 2022

Preprint

View full text Add to dashboard Cite

The insect steroid hormone ecdysone plays a critical role in insect development. Several recent studies have shown that ecdysone is transported through Organic Anion Transporting Polypeptides (OATPs) in insects such as flies and mosquitoes. However, the conservation of this mechanism across other arthropods and the role of this transporter in canonical ecdysone pathways are less well studied. Herein we functionally characterized the putative ecdysone transporter OATP74D from two major agricultural moth pests: Helicoverpa armigera (cotton bollworm) and Spodoptera frugiperda (fall armyworm). Phylogenetic analysis of OATP transporters across the superphylum Ecdysozoa revealed that Oatp74D is well represented among arthropod species and appeared only at the root of the arthropod lineage. Partial disruption of Oatp74D in S. frugiperda decreased embryo hatching rate and larval survival, suggesting that this gene is essential for development in vivo. Depletion and re-expression of OatP74D in the lepidoptera cell line RP-HzGUT-AW1(MG) confirmed the gene’s role in ecdysone import and demonstrated that OATP74D is essential for the transcriptional activation of ecdysone responsive genes including caspase-3, implicating this transporter in cell death pathways. Establishment of a simple and robust luciferase assay using the RP-HzGUT- AW1(MG) cell line demonstrated that both HaOATP74D and SfOATP74D are inhibited by rifampicin, a well-known organic anion transporter inhibitor. Overall, this work sheds more light on ecdysone uptake mechanisms across insect species and broadens our knowledge of the physiological roles of OATPs in the transportation of endogenous substrates.Author SummaryThe insect steroid hormone ecdysone is critical in regulating many aspects of insects’ life, including development and reproduction. A passive diffusion model was never functionally resolved, but was strongly supported until an organic anion transporting polypeptide was identified to mediate the transport of the hormone. The OATP74D, belonging to the Solute carrier superfamily, has been identified and functionally characterized for the first time in Drosophila melanogaster. Although phylogenetic analysis suggests that the Drosophila Oatp74D is probably conserved among several insect species, the theory for transporter mediated ecdysone uptake cannot be generalized to all insects without concrete proof. In here we provide functional evidence that the Oatp74D of two lepidopteran pest species: Helicoverpa armigera and Spodoptera frugiperda, is highly required for insect survival and development. Furthermore, we reveal that the OATP74D is necessary to regulate the expression of several ecdysone response genes, including caspase-3 which is involved in programmed cell death. In addition, we have developed a cell-based platform for screening chemical compounds against the lepidopteran orthologs of Oat74D and rifampicin was functionally shown to inhibit ecdysone uptake. Taken all together, our study reveals that Oatp74D is conserved among several arthropod species in the ecdysone pathway and given the high necessity for an effective control of these two lepidopteran species, we hypothesized that OATP74D could serve as a possible drug target in those two species.

show abstract

Section: Oatp74d Is Essential For Lepidopteran Insect Development And...supporting

confidence: 92%

Functional characterization of putative ecdysone transporters in lepidopteran pests

Samantsidis

Fotiadou

Tzavellas

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Recent studies in Drosophila have shown that ecdysone, the primary steroid hormone in insects, requires a membrane transporter EcI to enter its target cells and exert its genomic effects through EcR (6, 25). Although this critical function of EcI in ecdysone signaling seems to be highly conserved among other insect species (7), we noticed that EcI orthologs are unexpectedly missing in mosquitoes. In the present study, we characterized additional ecdysone importers, EcI-2, 3, and 4, in both Drosophila and Aedes .…”

Section: Discussionmentioning

confidence: 74%

“…Although it has long been assumed that ecdysone can pass through the cell membrane through simple diffusion, we recently demonstrated that an organic anion-transporting polypeptide (OATP), which we named Ecdysone Importer (EcI), is required for cellular uptake of ecdysone in the fruit fly Drosophila melanogaster (6). EcI orthologs are found among a wide variety of insects (6), and it is likely that its critical function as a mediator of ecdysone signaling is highly conserved in other insect species (7).…”

Section: Introductionmentioning

confidence: 99%

Essential functions of mosquito ecdysone importers in development and reproduction

Hun

Okamoto

Imura

et al. 2021

Preprint

View full text Add to dashboard Cite

The primary insect steroid hormone ecdysone requires a membrane transporter to enter its target cells. Although an organic anion-transporting polypeptide (OATP) named Ecdysone Importer (EcI) serves this role in the fruit fly Drosophila melanogaster and most likely in other arthropod species, this highly conserved transporter is apparently missing in mosquitoes. Here we report three additional OATPs that facilitate cellular incorporation of ecdysone in Drosophila and the yellow fever mosquito Aedes aegypti. These additional ecdysone importers (EcI-2, 3, and 4) are dispensable for development and reproduction in Drosophila, consistent with the predominant role of EcI. In contrast, in Aedes, EcI-2 is indispensable for ecdysone-mediated development, whereas EcI-4 is critical for vitellogenesis induced by ecdysone in adult females. Altogether, our results indicate unique and essential functions of these additional ecdysone importers in mosquito development and reproduction, making them attractive molecular targets for species- and stage-specific control of ecdysone signaling in mosquitoes.

show abstract

“…Because TcABCC‐5V was particularly strongly upregulated in the fat body, it was suggested that this transporter has a function in the export of DFB metabolites (possibly conjugated with glutathione) generated in fat body cells (Rösner & Merzendorfer, 2020). Interestingly, the import of DFB into fat body cells appears to be mediated by the organic anion transporter TcOATP5‐A1.1 , because the expression is strongly upregulated in response to DFB in the fat body and RNAi‐mediated gene silencing of TcOATP5‐A1.1 results in increased susceptibility to the insecticide (Rösner et al ., 2021).…”

Section: Discussionmentioning

confidence: 99%

Identification of two ABCC transporters involved in malathion detoxification in the red flour beetle, Tribolium castaneum

Rösner

Merzendorfer

2021

Insect Science

Self Cite

View full text Add to dashboard Cite

ABC transporters have been suggested to be involved in insecticide detoxification in different insect species mainly based on the indirect observation of transcriptional upregulation of ABC gene expression in response to insecticide exposure. Previous studies performed by us and others in the red flour beetle, Tribolium castaneum, have analyzed the function of TcABCA‐C and TcABCG‐H genes using RNA interference (RNAi) and demonstrated that specific TcABCA and TcABCC genes are involved in the elimination of the pyrethroid tefluthrin and the benzoylurea diflubenzuron, because gene silencing increased the beetle's susceptibility to the insecticides. In this study, we focused on the potential functions of TcABCA‐C genes in detoxification of the pyrethroid cyfluthrin (CF), the organophosphate malathion (MAL) and the diacylhdyazine tebufenozide (TBF). Analysis of transcript levels of selected TcABCA‐C genes in response to treatment with these three chemically unrelated insecticides revealed that some genes were particularly upregulated after insecticide treatment. In addition, the ABC inhibitor verapamil synergized significantly the toxicity of MAL but only negligibly CF and TBF toxicities. Finally, silencing of two TcABCC genes by RNAi revealed a significant increase in susceptibility to MAL. In contrast, we did not observe a significant increase in insecticide‐induced mortalities when knocking down TcABC genes in larvae treated with CF or TBF, although they were upregulated in response to insecticide treatment. Our results suggest that two pleiotropic ABCC transporters expressed in metabolic and excretory tissues contribute to the elimination of MAL.

show abstract

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

Cited by 9 publications

References 33 publications

Functional characterization of putative ecdysone transporters in lepidopteran pests

Functional characterization of putative ecdysone transporters in lepidopteran pests

Essential functions of mosquito ecdysone importers in development and reproduction

Identification of two ABCC transporters involved in malathion detoxification in the red flour beetle, Tribolium castaneum

Contact Info

Product

Resources

About