The ligand-gated chloride channel gene family of Drosophila melanogaster

The antagonism of cellular excitability in insects is mediated by a family of ionotropic receptors, the ligand-gated chloride channels. In insects these inhibitory receptors include synaptic GABA and histamine receptors, functionally analogous to vertebrate GABA and glycine receptors, and glutamate receptors that appear to be unique to invertebrates. The ligand-gated chloride channel family in insects includes two well-validated targets for insect control agents: GABA receptors, which are the targets for a structural variety of small-molecule insecticides (polychlorocycloalkanes such as dieldrin and phenylpyrazoles such as fipronil) that have been used widely in agriculture; and glutamate receptors, which are the targets of macrocyclic lactone natural products (the avermectins) that have yielded not only commercial insecticides but also anthelminthic agents (i.e., ivermectin) employed in animal and human health. The availability of the complete genome sequence of the insect model system Drosophila melanogaster has permitted the identification of all of the genes encoding proteins with structural similarity to known ligand-gated chloride channel subunits (ligand-gated chloride channel homologs or LCCHs). Here, we review the present status of knowledge of the structure and function of the proteins encoded by this compact gene family. The 12 LCCH genes of D. melanogaster exhibit a surprising degree of structural diversity, which is further enhanced for some subunits by a variety of post-transcriptional and post-translational modifications. Although the structures of the gene products encoded by this small gene family are now well characterized, surprisingly little is known of the biological functions of the majority of them and the structures of most native receptors remain unknown.