Insects
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2025
·Vol. 16
·期 5
·479
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IF 2.9
Xiangyi Zhou,Guoxing Chen,Keying Chen,Zhanyi Xu,Jiali Qian,Ru Yan,Bosheng Chen,Huiming Wu,Mengli Chen
Simple SummaryBactrocera dorsalis(Hendel) (Diptera: Tephritidae), a highly invasive pest with high transmissibility and adaptability, causes severe damage to various commercial vegetables and fruits. RDL, as the homomeric subunit of γ-aminobutyric acid (GABA) receptors, is the target of several insecticides. In this study, we found thatBdRdlwas highly expressed in the pupae and heads of male and female adult insects. Also, BdRDL was functionally characterized inXenopus oocytesby two-electrode voltage clamping and we found that fluralaner worked as an antagonist of BdRDL. Furthermore, we found that fluralaner exhibited a comparable insecticidal activity to avermectin againstB. dorsalisadults. Finally, the modeling and molecular docking predicted that fluralaner interacted with BdRDL via hydrogen bonds. These results suggested that fluralaner, as an antagonist of BdRDL, could be used to controlB. dorsalis.Bactrocera dorsalis(Hendel) (Diptera: Tephritidae), a highly destructive pest, affects fruits and vegetables globally, leading to significant economic losses. As a homomeric subunit of γ-aminobutyric acid (GABA) receptors, RDL plays a crucial role in various physiological activities in insects. However, functional characterization of RDL fromB. dorsalishas not yet been elucidated. Here, we cloned theRdlgene fromB. dorsalis,BdRdl, and investigated the expression pattern ofBdRdl. The results showed thatBdRdlwas highly expressed in pupae and the heads of male and female adults. Also, we characterized the BdRDL inXenopus oocytesthrough two-electrode voltage clamping. It turned out that the inward current of BdRDL induced by GABA was followed in a dose-dependent manner with a median effective concentration (EC50) of 2.4 × 10−4M. Additionally, we determined the mode action of fluralaner, a new insecticide, on BdRDL in oocytes. We found that fluralaner significantly inhibited the currents induced by GABA, suggesting that fluralaner worked as an antagonist of BdRDL. Furthermore, we found that fluralaner exhibited a comparable insecticidal activity to avermectin againstB. dorsalisadults. Lastly, the modeling and molecular docking predicted that fluralaner interacted with RDL via hydrogen bonds. Our results not only characterized the RDL ofB. dorsalis, but also revealed that fluralaner works as an antagonist of BdRDL and could be used as an effective strategy forB. dorsaliscontrol.
研究领域:
昆虫学
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分子生物学
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PubMed
高影响因子
Nature Ecology & Evolution
·
2023
·Vol. 7
·期 9
·1444-1456
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IF 16.8
Guo Lei,Qiao Xiaomu,Haji Diler,Zhou Tianhao,Liu Zhihan,Whiteman Noah K.,Huang Jia
The molecular mechanisms of coevolution between plants and insects remain elusive. GABA receptors are targets of many neurotoxic terpenoids, which represent the most diverse array of natural products known. Over deep evolutionary time, as plant terpene synthases diversified in plants, so did plant terpenoid defence repertoires. Here we show that herbivorous insects and their predators evolved convergent amino acid changing substitutions in duplicated copies of the Resistance to dieldrin ( Rdl ) gene that encodes the GABA receptor, and that the evolution of duplicated Rdl and terpenoid-resistant GABA receptors is associated with the diversification of moths and butterflies. These same substitutions also evolved in pests exposed to synthetic insecticides that target the GABA receptor. We used in vivo genome editing in Drosophila melanogaster to evaluate the fitness effects of each putative resistance mutation and found that pleiotropy both facilitates and constrains the evolution of GABA receptor resistance. The same genetic changes that confer resistance to terpenoids across 300 Myr of insect evolution have re-evolved in response to synthetic analogues over one human lifespan.
研究领域:
分子生物学
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进化生物学
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昆虫学
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PubMed
高影响因子
PEST MANAGEMENT SCIENCE
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2023
·
IF 4.1
Xiaomu Qiao,Tianhao Zhou,Jing Zhang,Lixin Zhang,Yaobin Lu,Jia Huang
BACKGROUND Insect RDL (resistant to dieldrin) receptors are essential pentameric ligand-gated chloride channels that mediate the neuroinhibitory effect of GABA, the chief inhibitory neurotransmitter in the central nervous system. These receptors serve as primary targets for various insecticides, including noncompetitive antagonists (NCAs) such as cyclodiene organochlorines and phenylpyrazoles, as well as allosteric modulators like meta-diamides and isoxazolines. This study focuses on a newly discovered A2′N mutation within the RDL receptors, identified in fipronil-resistant planthoppers. Despite in vitro electrophysiological studies have proposed its role in conferring target-site resistance, in vivo genetic functional validation of this mutation remains unexplored. RESULTS Our research employed toxicity bioassays, assessing various Rdl genotypes against a spectrum of insecticides, including fipronil, α-endosulfan, broflanilide, and isocycloseram. Results revealed distinct resistance profiles for A2′N and A2′S mutants, indicating different binding interactions of RDL receptors with NCAs. Significantly, the A2′N heterozygote showed substantial resistance to fipronil, despite its homozygous lethality. Molecular modeling and docking simulations further supported these findings, highlighting unique binding poses for fipronil and α-endosulfan. CONCLUSION This study confirmed that A2′N mutation of the RDL GABA receptor confer high resistance to fipronil in vivo . The observed resistance in A2′N mutants is likely attributable to a steric hindrance mechanism, wherein the introduction of larger side chains hampers fipronil binding, even in a heterozygous state. © 2023 Society of Chemical Industry.
研究领域:
昆虫学
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神经生物学
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毒理学
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Zhong Qiang Jia,Su Gui Zhang,Ying Wang,Jun Heng Pan,Fei Fan Liu,En Ling Zhan,Eman Atef Fouad,Ya Li Fu,Qi Rui Pan,Chun Qing Zhao
In insect ionotropic γ-aminobutyric acid receptor (iGABAR) subunits, only resistance to dieldrin (RDL) can be individually and functionally expressed in vitro. In lepidopteran, two to three RDL subtypes are identified; however, their physiological roles have not been distinguished in vivo. In this study, SlRdl1 and SlRdl2 of S. litura were individually knocked out using CRISPR/Cas9, respectively. The mortality and larval and pupal duration of KOSlRdl1 and KOSlRdl2 were increased. The flight time and distance were increased by 43.30%–80.66% and 58.96%–198.22%, respectively, in KOSlRdl1. The GABA-induced current was significantly decreased by 53.57%–74.28% and 46.91%–63.34% in the ventral nerve cord, and the GABA titer was significantly reduced by 17.65%–28.05% and 19.85%–42.46% in KOSlRdl1 and KOSlRdl2, respectively. In conclusion, SlRdl1 and SlRdl2 are necessary for the transmission of GABA-induced neural signals; however, only SlRdl1 could regulate the flight capability of S. litura. Our results provided a new avenue to study lepidopteran iGABARs.
研究领域:
昆虫学
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分子生物学
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神经科学
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基因工程
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PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2023
·
IF 4.7
Yihan Yu,Dandan Tian,Sanghyok Ri,Tongchol Kim,Kwangjin Ju,Jiongming Zhang,Shuangshuang Teng,Weixia Zhang,Wei Shi,Guangxu Liu
Although accumulating data demonstrated that gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter , plays an important regulatory role in immunity of vertebrates, its immunomodulatory function and mechanisms of action remain poorly understood in invertebrates such as bivalve mollusks . In this study, the effect of GABA on phagocytic activity of hemocytes was evaluated in a commercial bivalve species, Tegillarca granosa . Furthermore, the potential regulatory mechanism underpinning was investigated by assessing potential downstream targets. Data obtained demonstrated that in vitro GABA incubation significantly constrained the phagocytic activity of hemocytes. In addition, the GABA-induced suppression of phagocytosis was markedly relieved by blocking of GABA A and GABA B receptors using corresponding antagonists. Hemocytes incubated with lipopolysaccharides (LPS) and GABA had significant higher K + -Cl - cotransporter 2 (KCC2) content compared to the control. In addition, GABA treatment led to an elevation in intracellular Cl − , which was shown to be leveled down to normal by blocking the ionotropic GABA A receptor. Treatment with GABA A receptor antagonist also rescued the suppression of GABA A receptor-associated protein ( GABARAP ), KCC , TNF receptor associated factor 6 ( TRAF6 ), inhibitor of nuclear factor kappa-B kinase subunit alpha ( IKKα ), and nuclear factor kappa B subunit 1 ( NFκB ) caused by GABA incubation. Furthermore, incubation of hemocytes with GABA resulted in a decrease in cAMP content, an increase in intracellular Ca 2+ , and downregulation of cAMP-dependent protein kinase ( PKA ), calmodulin kinase II ( CAMK2 ), calmodulin ( CaM ), calcineurin ( CaN ), TRAF6 , IKKα , and NFκB . All these above-mentioned changes were found to be evidently relieved by blocking the metabotropic G-protein-coupled GABA B receptor. Our results suggest GABA may play an inhibitory role on phagocytosis through binding to both GABA A and GABA B receptors, and subsequently regulating corresponding downstream pathways in bivalve invertebrates.
研究领域:
免疫学
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分子生物学
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海洋生物学
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无脊椎动物生理学
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PubMed
高影响因子
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