ALTERNATIVE SPLICING OF A CAENORHABDITIS-ELEGANS GENE PRODUCES 2 NOVEL INHIBITORY AMINO-ACID RECEPTOR SUBUNITS WITH IDENTICAL LIGAND-BINDING DOMAINS BUT DIFFERENT ION CHANNELS

Two full-length cDNAs, gbr-2A and gbr-2B, encoding inhibitory amino ac id receptor subunits have been amplified and cloned from Caenorhabditi s elegans mRNA. The 5' 732 bp of the two cDNAs, encoding 237 amino aci ds, are identical. The 3' 758 bp of the gbr-2B cDNA are present within the 3' untranslated region of the gbr-2A clone. As a result, the two cDNAs are predicted to encode subunits which share a common extracellu lar N-terminal sequence of 237 amino acids, but different, though clos ely related, C-terminal sequences which include four predicted membran e-spanning regions. A search of the EMBL database revealed that the se quences of the two subunits are most closely related to the alpha-subu nit of the C. elegans avermectin receptor. Northern blot analysis show ed the presence of two related mRNAs of approximately 2.2 and 1.5 kb i n a developmentally mixed population of C. elegans. The genomic DNA se quence confirms that both mRNAs were transcribed from the same gene, g br-2, suggesting that the closely related 3' sequences have arisen as a result of a partial gene duplication event. We propose that C. elega ns is utilising alternative splicing to generate receptor subunits wit h identical extracellular, ligand-binding domains but different transm embrane, channel forming domains. (C) 1997 Elsevier Science B.V.