title: Pleiotropic Effects of Loss of the Dα1 Subunit in Drosophila melanogaster: Implications for Insecticide Resistance.
abstract: Nicotinic acetylcholine receptors (nAChRs) are a highly conserved gene family that form pentameric receptors involved in fast excitatory synaptic neurotransmission. The specific roles individual nAChR subunits perform in Drosophila melanogaster and other insects are relatively uncharacterized. Of the 10 D. melanogaster nAChR subunits, only three have described roles in behavioral pathways; Dα3 and Dα4 in sleep, and Dα7 in the escape response. Other subunits have been associated with resistance to several classes of insecticides. In particular, our previous work has demonstrated that an allele of the Dα1 subunit is associated with resistance to neonicotinoid insecticides. We used ends-out gene targeting to create a knockout of the Dα1 gene to facilitate phenotypic analysis in a controlled genetic background. To our knowledge, this is the first report of a native function for any nAChR subunits known to be targeted by insecticides. Loss of Dα1 function was associated with changes in courtship, sleep, longevity, and insecticide resistance. While acetylcholine signaling had previously been linked with mating behavior and reproduction in D. melanogaster, no specific nAChR subunit had been directly implicated. The role of Dα1 in a number of behavioral phenotypes highlights the importance of understanding the biological roles of nAChRs and points to the fitness cost that may be associated with neonicotinoid resistance.
authors.affiliation: School of BioSciences, University of Melbourne, Victoria 3010, Australia.|Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Somers
authors.affiliation: School of BioSciences, University of Melbourne, Victoria 3010, Australia.|Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia.
authors.forename: Hang Ngoc Bao
authors.initials: HN
authors.lastname: Luong
authors.affiliation: School of BioSciences, University of Melbourne, Victoria 3010, Australia.|Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia.
authors.forename: Judith
authors.initials: J
authors.lastname: Mitchell
authors.affiliation: School of BioSciences, University of Melbourne, Victoria 3010, Australia.|Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Batterham
authors.affiliation: School of BioSciences, University of Melbourne, Victoria 3010, Australia trentp@unimelb.edu.au.|Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia trentp@unimelb.edu.au.
authors.forename: Trent
authors.initials: T
authors.lastname: Perry
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000691:Anabasine / Q000494:pharmacology; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology; D008297:Male; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D007306:Insecticides; D011978:Receptors, Nicotinic; C113681:nicotinic acetylcholine receptor alpha-subunits, Drosophila; D000691:Anabasine; D000109:Acetylcholine
keywords: behavior; neonicotinoids; nicotinic acetylcholine receptors; resistance; sleep