Cloning of the Drosophila cyclodiene insecticide resistance gene: a novel GABAA receptor subtype?

1. gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in both vertebrates and invertebrates. GABAA receptors are composed of a number of different subunits that assemble to form a chloride ionophore. 2. Several subunit types, alpha, beta, gamma, delta and rho have been cloned from vertebrates, but until recently these receptors have remained uncloned from invertebrates. 3. GABAA receptors form the proposed site of action of cyclodiene insecticides. Therefore a Drosophila mutant (Rdl), resistant to cyclodienes and the GABAA receptor ligand picrotoxin (PTX), was used to clone the gene responsible for resistance as a putative invertebrate GABAA receptor. 4. Analysis of the predicted amino acid sequence and gene structure shows that Rdl codes for a receptor subunit similar to vertebrate GABAA receptors, but sufficiently different that it may represent a novel class of GABAA receptor subtype. 5. Cyclodiene insecticide resistance accounts for over 60% of reported cases of insecticide resistance and is also found in vertebrates. 6. Therefore elucidating the molecular basis of cyclodiene resistance is not only important to our understanding of pesticide action on the GABAA receptor but also in examining the conservation of the resistance mechanism between vertebrates and invertebrates.