SEQUENCE OF A DROSOPHILA LIGAND-GATED ION-CHANNEL POLYPEPTIDE WITH ANUNUSUAL AMINO-TERMINAL EXTRACELLULAR DOMAIN

We report the isolation of a full-length clone from a Drosophila melan ogaster head cDNA library that encodes a 614-residue polypeptide that exhibits all of the features of a ligand-gated chloride-channel/recept or subunit. This polypeptide, which has been named GRD (denoting that the polypeptide is a GABA(A) and glycine receptor-like subunit of Dros ophila), displays between 33 and 44% identity to vertebrate GABA(A) an d glycine receptor subunits and 32-37% identity to the GABA(A) recepto r-like polypeptides from Drosophila and Lymnaea. It is interesting tha t the large amino-terminal, presumed extracellular domain of the GRD p rotein contains an insertion, between the dicysteine loop and the firs t putative membrane-spanning domain, of 75 amino acids that is not fou nd in any other ligand-gated chloride-channel subunit. Analysis of cDN A and genomic DNA reveals that these residues are encoded by an extens ion of an exon that is equivalent to exon 6 of vertebrate GABA(A) and glycine receptor genes. The gene (named Grd) that encodes the Drosophi la polypeptide has been mapped, bu in situ hybridization, to position 75A on theleft arm of chromosome 3.