SER-7, a Caenorhabditis elegans 5-HT7-like receptor, is essential for the 5-HT stimulation of pharyngeal pumping and egg laying

Genetics. 2006 Jan;172(1):159-69. doi: 10.1534/genetics.105.044495. Epub 2005 Oct 3.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Behavior, Animal
  • COS Cells
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism
  • Chlorocebus aethiops
  • Female
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • Ligands
  • Motor Neurons / metabolism
  • Muscles / physiology
  • Oviposition / drug effects
  • Oviposition / physiology*
  • Pharynx / drug effects
  • Pharynx / metabolism*
  • Phenotype
  • Receptors, Serotonin, 5-HT2 / chemistry
  • Receptors, Serotonin, 5-HT2 / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism
  • Serotonin / pharmacology*
  • Signal Transduction
  • Tryptophan Hydroxylase / chemistry
  • Tryptophan Hydroxylase / metabolism
  • Vulva / physiology

Substances

  • Caenorhabditis elegans Proteins
  • EGL-1 protein, C elegans
  • Ligands
  • Receptors, Serotonin, 5-HT2
  • Repressor Proteins
  • SER-7b protein, C elegans
  • Serotonin
  • TPH1 protein, human
  • Tryptophan Hydroxylase
  • GTP-Binding Protein alpha Subunits, Gs
  • Adenylyl Cyclases