Characterization of a novel serotonin receptor from Caenorhabditis elegans: Cloning and expression of two splice variants

Serotonin [5-hydroxytryptamine (5-HT)] modulates feeding activity, egg-layi ng, and mating behavior in the free-living nematode, Caenorhabditis elegans . We have cloned a novel receptor cDNA from C. elegans (5-HT2Ce)that has hi gh sequence homology with 5-HT2 receptors from other species. When transien tly expressed in COS-7 cells, 5-HT2Ce exhibited 5-HT binding activity and a ctivated Ca2+-mediated signaling in a manner analogous to other 5-HT2 recep tors, However, 5-HT2Ce displayed unusual pharmacological properties, which resembled both 5-HT2 and 5-HT1-like receptors but did not correlate well wi th any of the known 5-HT2 subtypes. Two splice variants of 5-HT2Ce that dif fer by 48 id-terminal amino acids were identified. The two isoforms were fo und to have virtually identical binding and signaling properties but differ ed in their levels of mRNA expression, with the longer variant being four t imes more abundant than the shorter species in all developmental stages tes ted. Taken together, the results describe two Variants of a novel C, elegan s 5-HT receptor, which has some of the properties of the 5-HT2 family but w hose pharmacological profile does not conform to any known class of recepto r.