RRC ID 3393
Author Norman KR, Fazzio RT, Mellem JE, Espelt MV, Strange K, Beckerle MC, Maricq AV.
Title The Rho/Rac-family guanine nucleotide exchange factor VAV-1 regulates rhythmic behaviors in C. elegans.
Journal Cell
Abstract 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+).
Volume 123(1)
Pages 119-32
Published 2005-10-7
DOI 10.1016/j.cell.2005.08.001
PII S0092-8674(05)00803-2
PMID 16213217
MeSH 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
IF 36.216
Times Cited 40
C.elegans tm402