Insect GABA receptors: splicing, editing, and targeting by antiparasitics and insecticides.
Ionotropic GABA receptors are abundant in both vertebrate and invertebrate nervous systems, where they mediate rapid, mostly inhibitory synaptic transmission. A GABA-gated chloride channel subunit from Drosophila melanogaster [Resistant to Dieldrin (RDL)] has been cloned, functionally expressed, and found to exhibit many aspects of the pharmacology of native, bicuculline-insensitive insect GABA receptors. RDL is the target of the commercially important insecticide fipronil. A point mutation in the channel-lining region of the RDL molecule is known to underlie most cases of resistance to insecticides acting on GABA receptors. RDL is widely distributed throughout the insect nervous system, but the subunit composition of RDL-containing in native receptors is unknown. It is possible that in some instances, RDL coexpresses with glutamate-gated chloride channel subunits. Other ionotropic receptor subunits (LCCH3 and GRD) form GABA-gated cation channels when heterologously expressed. Interest in RDL as a model ligandgated anion channel has been enhanced by the recent discovery of pre-mRNA A-to-I editing, which, together with alternative splicing, adds to the functional diversity of this GABA receptor subunit.
Buckingham
Steven David
SD
Medical Research Council Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, UK.
Biggin
Philip Charles
PC
Sattelle
Benedict Mark
BM
Brown
Laurence Andrew
LA
Sattelle
David Barry
DB
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004331:Drosophila melanogaster; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D008969:Molecular Sequence Data; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics; D018079:Receptors, GABA / Q000187:drug effects / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D000981:Antiprotozoal Agents; D007306:Insecticides; D012333:RNA, Messenger; D018079:Receptors, GABA