The Rho/Rac-family guanine nucleotide exchange factor VAV-1 regulates rhythmic behaviors in C. elegans

Cell. 2005 Oct 7;123(1):119-32. doi: 10.1016/j.cell.2005.08.001.


Rhythmic behaviors are a fundamental feature of all organisms. Pharyngeal pumping, the defecation cycle, and gonadal-sheath-cell contractions are three well-characterized rhythmic behaviors in the nematode C. elegans. The periodicities of the rhythms range from subsecond (pharynx) to seconds (gonadal sheath) to minutes (defecation). However, the molecular mechanisms underlying these rhythmic behaviors are not well understood. Here, we show that the C. elegans Rho/Rac-family guanine nucleotide exchange factor, VAV-1, which is homologous to the mammalian Vav proto-oncogene, has a crucial role in all three behaviors. vav-1 mutants die as larvae because VAV-1 function is required in the pharynx for synchronous contraction of the musculature. In addition, ovulation and the defecation cycle are abnormal and arrhythmic. We show that Rho/Rac-family GTPases and the signaling molecule inositol triphosphate (IP(3)) act downstream of VAV-1 signaling and that the VAV-1 pathway modulates rhythmic behaviors by dynamically regulating the concentration of intracellular Ca(2+).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Behavior, Animal / physiology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / isolation & purification
  • Caenorhabditis elegans Proteins / metabolism*
  • Calcium Signaling / genetics
  • Conserved Sequence / genetics
  • Defecation / genetics
  • Feeding Behavior / physiology
  • Gene Expression Regulation / genetics
  • Inositol Phosphates / metabolism
  • Molecular Sequence Data
  • Mutation / genetics
  • Ovulation / genetics
  • Periodicity*
  • Peristalsis / genetics
  • Proto-Oncogene Proteins c-vav / genetics
  • Proto-Oncogene Proteins c-vav / isolation & purification
  • Proto-Oncogene Proteins c-vav / metabolism*
  • Signal Transduction / genetics
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism


  • Caenorhabditis elegans Proteins
  • Inositol Phosphates
  • Proto-Oncogene Proteins c-vav
  • VAV-1 protein, C elegans
  • inositol-1,5,6-triphosphate
  • rho GTP-Binding Proteins