Functional Characteristics of the Lepidopteran Ionotropic GABA Receptor 8916 Subunit Interacting with the LCCH3 or the RDL Subunit,Journal of Agricultural and Food Chemistry

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Functional Characteristics of the Lepidopteran Ionotropic GABA Receptor 8916 Subunit Interacting with the LCCH3 or the RDL Subunit
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2021-09-23 , DOI: 10.1021/acs.jafc.1c00385
Qiu Tang Huang ₁ , Cheng Wang Sheng ₁ , Andrew K Jones ₂ , Jie Jiang ₁ , Tao Tang ₃ , Zhao Jun Han ₁ , Chun Qing Zhao ₁

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The ionotropic γ-aminobutyric acid (iGABA) receptor is commonly considered as a fast inhibitory channel and is an important insecticide target. Since 1990, RDL, LCCH3, and GRD have been successively isolated and found to be potential subunits of the insect iGABA receptor. More recently, one orphan gene named 8916 was found and considered to be another potential iGABA receptor subunit according to its amino acid sequence. However, little information about 8916 has been reported. Here, the 8916 subunit from Chilo suppressalis was studied to determine whether it can form part of a functional iGABA receptor by co-expressing this subunit with CsRDL1 or CsLCCH3 in the Xenopus oocyte system. Cs8916 or CsLCCH3 did not form functional ion channels when expressed alone. However, Cs8916 was able to form heteromeric ion channels when expressed with either CsLCCH3 or CsRDL1. The recombinant heteromeric Cs8916/LCCH3 channel was a cation-selective channel, which was sensitive to GABA or β-alanine. The current of the Cs8916/LCCH3 channel was inhibited by dieldrin, endosulfan, fipronil, or ethiprole. In contrast, fluralaner, broflanilide, and avermectin showed little effect on the Cs8916/LCCH3 channel (IC₅₀s > 10 000 nM). The Cs8916/RDL1 channel was sensitive to GABA, but was significantly different in EC₅₀ and I_max for GABA to those of homomeric CsRDL1. Fluralaner, fipronil, or dieldrin showed antagonistic actions on Cs8916/RDL1. In conclusion, Cs8916 is a potential iGABA receptor subunit, which can interact with CsLCCH3 to generate a cation-selective channel that is sensitive to several insecticides. Also, as Cs8916/RDL1 has a higher EC₅₀ than homomeric CsRDL1, Cs8916 may affect the physiological functions of CsRDL1 and therefore play a role in fine-tuning GABAergic signaling.

中文翻译：

鳞翅目离子型 GABA 受体 8916 亚基与 LCCH3 或 RDL 亚基相互作用的功能特征

离子型γ-氨基丁酸（iGABA）受体通常被认为是一种快速抑制通道，是重要的杀虫剂靶点。自 1990 年以来，RDL、LCCH3 和 GRD 相继被分离出来并被发现是昆虫 iGABA 受体的潜在亚基。最近，发现了一个名为 8916 的孤儿基因，根据其氨基酸序列，它被认为是另一种潜在的 iGABA 受体亚基。然而，关于 8916 的信息却鲜有报道。在这里，研究了来自Chilo suppressalis的 8916 亚基，以确定它是否可以通过在非洲爪蟾卵母细胞中与 CsRDL1 或 CsLCCH3 共表达该亚基来形成功能性 iGABA 受体的一部分系统。Cs8916 或 CsLCCH3 在单独表达时不形成功能性离子通道。然而，当用 CsLCCH3 或 CsRDL1 表达时，Cs8916 能够形成异聚离子通道。重组异聚 Cs8916/LCCH3 通道是阳离子选择性通道，对 GABA 或 β-丙氨酸敏感。Cs8916/LCCH3 通道的电流受到狄氏剂、硫丹、氟虫腈或乙虫腈的抑制。相比之下，氟拉纳、溴氟苯胺和阿维菌素对 Cs8916/LCCH3 通道几乎没有影响（IC ₅₀ s > 10 000 nM）。Cs8916/RDL1 通道对 GABA 敏感，但在 EC ₅₀和I _{max 中}显着不同GABA 与同源 CsRDL1 的那些。Fluralaner、氟虫腈或狄氏剂对 Cs8916/RDL1 显示出拮抗作用。总之，Cs8916 是一个潜在的 iGABA 受体亚基，它可以与 CsLCCH3 相互作用产生一个对几种杀虫剂敏感的阳离子选择性通道。此外，由于 Cs8916/RDL1 的 EC ₅₀高于同源 CsRDL1，Cs8916 可能会影响 CsRDL1 的生理功能，因此在微调 GABA 能信号中发挥作用。

更新日期：2021-10-06

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