title: A spinosyn-sensitive Drosophila melanogaster nicotinic acetylcholine receptor identified through chemically induced target site resistance, resistance gene identification, and heterologous expression.
abstract: 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 Dalpha6. Subsequently, additional spinosyn-resistant alleles were generated by chemical mutagenesis and were also found to have mutations in the gene encoding Dalpha6, providing convincing evidence that Dalpha6 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 Dalpha6 alone, co-expression of Dalpha6 with an additional nAChR subunit, Dalpha5, and the chaperone protein ric-3 resulted in an acetylcholine- and spinosyn-sensitive receptor with the pharmacological properties anticipated for a native nAChR.
authors: Dow AgroSciences LLC, Discovery Research, 9330 Zionsville Road, Indianapolis, IN 46268, USA. gbwatson@dow.com
authors: Gerald B
authors: GB
authors: Watson
authors: Scott W
authors: SW
authors: Chouinard
authors: Kevin R
authors: KR
authors: Cook
authors: Chaoxian
authors: C
authors: Geng
authors: Jim M
authors: JM
authors: Gifford
authors: Gary D
authors: GD
authors: Gustafson
authors: James M
authors: JM
authors: Hasler
authors: Ignacio M
authors: IM
authors: Larrinua
authors: Ted J
authors: TJ
authors: Letherer
authors: Jon C
authors: JC
authors: Mitchell
authors: William L
authors: WL
authors: Pak
authors: Vincent L
authors: VL
authors: Salgado
authors: Thomas C
authors: TC
authors: Sparks
authors: Geoff E
authors: GE
authors: Stilwell
mesh_terms: D000818:Animals; D018833:Chaperonins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster; D004338:Drug Combinations; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics*; D015870:Gene Expression; D007306:Insecticides / Q000494:pharmacology*; D018942:Macrolides / Q000494:pharmacology*; D009154:Mutation; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D029721:Drosophila Proteins; D004338:Drug Combinations; D007306:Insecticides; D018942:Macrolides; D011978:Receptors, Nicotinic; C488972:nAChRalpha6 protein, Drosophila; C114883:spinosyn A; D018833:Chaperonins; C415329:spinosad; C548262:spinetoram