A new family of insect muscarinic acetylcholine receptors

Abstract

Most currently used insecticides are neurotoxic chemicals that target a limited number of sites and insect cholinergic neurotransmission is the major target. A potential target for insecticide development is the muscarinic acetylcholine receptor (mAChR), which is a metabotropic G-protein-coupled receptor. Insects have A- and B-type mAChRs and the five mammalian mAChRs are close to the A-type. We isolated a cDNA (CG12796) from the fruit fly, Drosophila melanogaster. After heterologous expression in Chinese hamster ovary K1 cells, CG12796 could be activated by acetylcholine [EC50 (half maximal effective concentration), 73 nM] and the mAChR agonist oxotremorine M (EC50 , 48.2 nM) to increase intracellular Ca(2+) levels. Thus, the new mAChR is coupled to Gq/11 but not Gs and Gi/o . The classical mAChR antagonists atropine and scopolamine N-butylbromide at 100 μM completely blocked the acetylcholine-induced responses. The orthologues of CG12796 can also be found in the genomes of other insects, but not in the genomes of the honeybee or parasitoid wasps. Knockdown of CG12796 in the central nervous system had no effect on male courtship behaviours. We suggest that CG12796 represents the first recognized member of a novel mAChR class.

Pre-synaptic Muscarinic Excitation Enhances the Discrimination of Looming Stimuli in a Collision-Detection Neuron

“…Two other muscarinic acetylcholine receptors types (m2 and m4) couple to G proteins of the G i/0 family, which leads to presynaptic or postsynaptic inhibition ( Caulfield, 1993 ; Brown, 2010 ). In flies and other arthropods, 3 types of muscarinic acetylcholine receptors have been found: types A, B, and C ( Xia et al, 2016 ). Type A resembles most of the vertebrate muscarinic acetylcholine receptors and is activated by acetylcholine and muscarine and blocked by atropine and scopolamine.…”

“…The type A muscarinic acetylcholine receptor is coupled to G q/11 type proteins, whereas type B is coupled to G i/0 ( Ren et al, 2015 ). Type C resembles type A ( Xia et al, 2016 ). Our results suggest that the muscarinic acetylcholine receptors presynaptic to the LGMD are either of type A or C. Their excitatory effects might result from inhibition of presynaptic M channels or other potassium channels ( Brown, 2010 ).…”

Muscarinic acetylcholine receptor signaling generates OFF selectivity in a simple visual circuit

“…Studies in mammalian mAchRs indicate that the excitatory M1/3 types are coupled to Gαq/11, whereas the inhibitory M2/4 types are coupled to Gαi/o 37 . The Drosophila genome contains three mAchRs, with types A and C coupling to Gαq/11 and type B coupling to Gαi/o 39,40 . Additionally, R72E03-Gal4, the enhancer Gal4 line labeling glu-lOLP, was generated using an upstream enhancer element identified in the Drosophila mAchR-B gene 28,29 , suggesting its expression in glu-lOLP.…”

Acetylcholine and Its Receptors in Honeybees: Involvement in Development and Impairments by Neonicotinoids

“…Both receptors have been identified in all arthropods with a sequenced genome [72]. Recently, a third (C-type) mAChR family has been described in D. melanogaster [73].…”