A spinosyn-sensitive Drosophila melanogaster nicotinic acetylcholine receptor identified through chemically induced target site resistance, resistance gene identification, and heterologous expression

被引:120
作者
Watson, Gerald B. [1 ]
Chouinard, Scott W. [2 ]
Cook, Kevin R. [3 ]
Geng, Chaoxian [1 ,4 ]
Gifford, Jim M. [1 ]
Gustafson, Gary D. [1 ]
Hasler, James M. [1 ]
Larrinua, Ignacio M. [1 ]
Letherer, Ted J. [1 ]
Mitchell, Jon C. [1 ]
Pak, William L. [4 ]
Salgado, Vincent L. [1 ]
Sparks, Thomas C. [1 ]
Stilwell, Geoff E. [2 ]
机构
[1] Dow AgroSci LLC, Discovery Res, Indianapolis, IN 46268 USA
[2] Cambria Pharmaceut, Woburn, MA 01801 USA
[3] Indiana Univ, Dept Biol, Bloomington Drosophila Stock Ctr, Bloomington, IN 47405 USA
[4] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA
基金
美国国家卫生研究院;
关键词
Spinosad; Spinetoram; Spinosyn; Resistance; Drosophila melanogaster; Nicotinic acetylcholine receptor (nAChR); Xeno pus laevis oocytes; Expression; Mode of action; ALPHA-SUBUNIT; D-ALPHA-6; BINDING; MODE; CLONING;
D O I
10.1016/j.ibmb.2009.11.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Strains of Drosophila melanogaster with resistance to the insecticides spinosyn A, spinosad, and spinetoram were produced by chemical mutagenesis. These spinosyn-resistant strains were not cross-resistant to other insecticides. The two strains that were initially characterized were subsequently found to have mutations in the gene encoding the nicotinic acetylcholine receptor (nAChR) subunit D alpha 6 Subsequently, additional spinosyn-resistant alleles were generated by chemical mutagenesis and were also found to have mutations in the gene encoding D alpha 6, providing convincing evidence that D alpha 6 is a target site for the spinosyns in D. melanogaster. Although a spinosyn-sensitive receptor could not be generated in Xenopus laevis oocytes simply by expressing D alpha 6 alone, co-expression of D alpha 6 with an additional nAChR subunit, D alpha 5, and the chaperone protein ric-3 resulted in an acetylcholine- and spinosyn-sensitive receptor with the pharmacological properties anticipated for a native nAChR. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:376 / 384
页数:9
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