Insect nicotinic acetylcholine receptors (nAChRs): Important amino acid residues contributing to neonicotinoid insecticides selectivity and resistance

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels which mediate fast cholinergic synaptic transmission in insect and vertebrate nervous systems. The great abundance of nAChRs within the insect central nervous system has led to the development of insecticides targeting these receptors, such as neonicotinoid insecticides. Neonicotinoid insecticides act selectively on insect nAChRs, accounting at least in part for the selective toxicity to insects over vertebrates. Some important amino acid residues in insect nAChR α and β subunits contribute to neonicotinoid insecticides selectivity, including important residues in loop C, the region loop B to the N-terminus and loop B-C interval of insect α subunit, and important residues in loop D, E and F of insect β subunit. Important residues contributing to neonicotinoid insecticides selectivity may also contribute to the resistance to these insecticides, if they mutate to other residues identical or similar to the corresponding residues in vertebrate subunits. The first point mutation Y151S has been identified in insect α subunit loop B to be associated with neonicotinoid insecticides resistance, which decreased neonicotinoid insecticides affinity remarkably, but showed little effects on insect nAChRs normal function.