Sun Haina, Buchon Nicolas, Scott Jeffrey G
Department of Entomology, Comstock Hall, Cornell University, Ithaca, NY, USA; Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, Jiangsu, China.
Department of Entomology, Comstock Hall, Cornell University, Ithaca, NY, USA.
Insect Biochem Mol Biol. 2017 Oct;89:11-16. doi: 10.1016/j.ibmb.2017.08.002. Epub 2017 Aug 10.
ABC transporters are ubiquitous membrane-bound proteins, present in both prokaryotes and eukaryotes. The major function of eukaryotic ABC transporters is to mediate the efflux of a variety of substrates (including xenobiotics) out of cells. ABC transporters have been widely investigated in humans, particularly for their involvement in multidrug resistance (MDR). Considerably less is known about their roles in transport and/or excretion in insects. ABC transporters are only known to function as exporters in insects. Drosophila melanogaster has 56 ABC transporter genes, including eight which are phylogenetically most similar to the human Mdr genes (ABCB1 clade). We investigated the role of ABC transporters in the ABCB1 clade in modulating the susceptibility to insecticides. We took advantage of the GAL4/UAS system in D. melanogaster to knockdown the expression levels of Mdr65, Mdr50, Mdr49 and ABCB6 using transgenic UAS-RNAi lines and conditional driver lines. The most notable effects were increased sensitivities to nine different insecticides by silencing of Mdr65. Furthermore, a null mutation of Mdr65 decreased the malathion, malaoxon and fipronil LC values by a factor of 1.9, 2.1 and 3.9, respectively. Altogether, this data demonstrates the critical role of ABC transporters, particularly Mdr65, in altering the toxicity of specific, structurally diverse, insecticides in D. melanogaster.
ABC转运蛋白是普遍存在的膜结合蛋白，存在于原核生物和真核生物中。真核生物ABC转运蛋白的主要功能是介导多种底物（包括外源性物质）从细胞中流出。ABC转运蛋白在人类中已得到广泛研究，特别是它们在多药耐药性（MDR）中的作用。而关于它们在昆虫体内运输和/或排泄中的作用，人们了解得相当少。目前已知ABC转运蛋白在昆虫中仅作为外排转运体发挥作用。黑腹果蝇有56个ABC转运蛋白基因，其中8个在系统发育上与人类Mdr基因（ABCB1进化枝）最为相似。我们研究了ABCB1进化枝中的ABC转运蛋白在调节对杀虫剂敏感性方面的作用。我们利用黑腹果蝇中的GAL4/UAS系统，通过转基因UAS-RNAi品系和条件驱动品系来降低Mdr65、Mdr50、Mdr49和ABCB6的表达水平。最显著的影响是通过沉默Mdr65增加了对9种不同杀虫剂的敏感性。此外，Mdr65的无效突变分别使马拉硫磷、马拉氧磷和氟虫腈的LC值降低了1.9倍、2.1倍和3.9倍。总之，这些数据证明了ABC转运蛋白，特别是Mdr65，在改变黑腹果蝇对特定的、结构多样的杀虫剂毒性方面的关键作用。
