title: SER-7, a Caenorhabditis elegans 5-HT7-like receptor, is essential for the 5-HT stimulation of pharyngeal pumping and egg laying.
abstract: Serotonin (5-HT) stimulates both pharyngeal pumping and egg laying in Caenorhabditis elegans. Four distinct 5-HT receptors have been partially characterized, but little is known about their function in vivo. SER-7 exhibits most sequence identity to the mammalian 5-HT7 receptors and couples to a stimulation of adenyl cyclase when expressed in COS-7 cells. However, many 5-HT7-specific agonists have low affinity for SER-7. 5-HT fails to stimulate pharyngeal pumping and the firing of the MC motorneurons in animals containing the putative ser-7(tm1325) and ser-7(tm1728) null alleles. In addition, although pumping on bacteria is upregulated in ser-7(tm1325) animals, pumping is more irregular. A similar failure to maintain "fast pumping" on bacteria also was observed in ser-1(ok345) and tph-1(mg280) animals that contain putative null alleles of a 5-HT2-like receptor and tryptophan hydroxylase, respectively, suggesting that serotonergic signaling, although not essential for the upregulation of pumping on bacteria, "fine tunes" the process. 5-HT also fails to stimulate egg laying in ser-7(tm1325), ser-1(ok345), and ser-7(tm1325) ser-1(ok345) animals, but only the ser-7 ser-1 double mutants exhibit an Egl phenotype. All of the SER-7 mutant phenotypes are rescued by the expression of full-length ser-7gfp translational fusions. ser-7gfp is expressed in several pharyngeal neurons, including the MC, M2, M3, M4, and M5, and in vulval muscle. Interestingly, 5-HT inhibits egg laying and pharyngeal pumping in ser-7 null mutants and the 5-HT inhibition of egg laying, but not pumping, is abolished in ser-7(tm1325);ser-4(ok512) double mutants. Taken together, these results suggest that SER-7 is essential for the 5-HT stimulation of both egg laying and pharyngeal pumping, but that other signaling pathways can probably fulfill similar roles in vivo.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hobson
authors.forename: Vera M
authors.initials: VM
authors.lastname: Hapiak
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.forename: Kara L
authors.initials: KL
authors.lastname: Buehrer
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Komuniecki
authors.forename: Richard W
authors.initials: RW
authors.lastname: Komuniecki
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D019556:COS Cells; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism; D002522:Chlorocebus aethiops; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D009046:Motor Neurons / Q000378:metabolism; D009132:Muscles / Q000502:physiology; D010058:Oviposition / Q000187:drug effects / Q000502:physiology*; D010614:Pharynx / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D044348:Receptors, Serotonin, 5-HT2 / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction; D014365:Tryptophan Hydroxylase / Q000737:chemistry / Q000378:metabolism; D014844:Vulva / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; C112486:EGL-1 protein, C elegans; D008024:Ligands; D044348:Receptors, Serotonin, 5-HT2; D012097:Repressor Proteins; C478614:SER-7b protein, C elegans; D012701:Serotonin; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases