Serotonin (5-HT) regulates a variety of key processes in nematodes, including feeding, pharyngeal pumping, locomotion and egg-laying. In Caenorhabditis elegans four distinct 5-HT receptors have been characterized, 5-HT1 (SER-4), 5-HT2 (SER-1) and 5-HT7 (SER-7)-like G-protein coupled receptors (GPCRs) that appear to couple to G45;i/o, G45;q and G45;s, respectively, as well as a novel 5-HT-gated Cl- channel (MOD-1), and we have recently identified homologues in Ascaris suum and Brugia malayi. Unfortunately, little is known about the function of the individual 5-HT receptors in vivo. Using a combination of C. elegans mutants and physiologicial assays in Ascaris suum , we have demonstrated that 5-HT fails to stimulate pharyngeal pumping in a putative null allele of a G45;scoupled receptor (SER-7) and egg-laying in both
ser-7(
tm1325) and
ser-1(
ok345), a putative null allele of a G45;qcoupled receptor (SER-1). In the absence of SER-7, 5-HT appears to fail to stimulate the firing of the MC motorneurons. In contrast, both
ser-7(
tm1325) and
ser-1(
ok345) animals appear to pump rapidly and lay eggs normally on bacteria. However, the up-regulation of pumping on bacteria in both mutants is more irregular than in wild type worms, suggesting that serotonergic signaling, although not essential, maintains and fine tunes the process. In
ser-7(
tm1325) and
ser-1(
ok345) animals, 5-HT dependent phenotypes are rescued with either full length
ser-7::gfp and
ser-1::gfp translation fusions. SER-7 appears to be expressed in several pharyngeal neurons (MC, M2, M3, M4, M5) and vulval muscle; SER-1 in 5 pairs of neurons in the nerve ring and pharyngeal and vulval muscle. In contrast, the expression of SER-7 in the M4 alone yields a stuffed pharynx phenotype and does not rescue 5-HT-stimulated pumping or egg-laying. The M4 appears to synapse onto the posterior half of the
pm5s, based on the M4 expression of synaptobrevin, suggesting that SER-7 expression in the M4 is probably involved with the regulation of isthmus peristalsis, not overall pumping. These results suggest that SER-7 is essential for the 5-HT stimulation of pharyngeal pumping and both SER-7 and SER-1 are essential for the 5-HT stimulation of egg-laying, but that other signaling pathways, perhaps mediated by neuropeptides, can fulfill similar regulatory roles in vivo.