Three functional isoforms of GAR-2, a Caenorhabditis elegans G-protein-linked acetylcholine receptor, are produced by alternative splicing

We have previously isolated a cDNA clone from Caenorhabditis elegans that e ncodes a novel form of G-protein-linked acetylcholine receptor, termed GAR- 2. GAR-2 is similar to but pharmacologically distinct from muscarinic acety lcholine receptors. Here we report the identification of two gar-2 cDNA clo nes that are different from the previous one. These newly identified cDNAs encode polypeptides of 664 and 627 amino acids, whereas the previous one en codes a polypeptide of 614 amino acids. The three GAR-2 isoforms, which dif fer only in the third intracellular loop, arise from alternative splicing. Electrophysiological analyses using the Xenopus oocyte system showed that a ll three GAR-2 isoforms couple to the activation of G-protein-gated inwardl y rectifying K+ (GIRK1) channel with similar drug specificity. Our results indicate that alternative splicing plays an important role in promoting mol ecular diversity of G-protein-linked acetylcholine receptors in C. elegans. (C) 2001 Academic Press.