VAV-1 is involved in rhythmic contraction events in C. elegans . Ken Norman , Rob Fazzio, Jerry Mellem, Mary Beckerle, Villu Maricq. Biology, University of Utah, Salt Lake City, UT.

The Vav family of guanine nucleotide exchange factors for the Rho/Rac GTPases has been implicated in many cellular processes. Namely, these exchange factors have been shown to regulate the cytoskeleton in response to extracellular signaling and they have been shown to function in creating intracellular Ca2+ fluxes. C. elegans contains one Vav family member, vav-1 . In C. elegans , vav-1 is expressed in most contractile tissue, including the pharynx, body wall muscle, gonadal sheath cells, as well as the spermatheca and rectal cells. To gain insight into the function of Vav, we have isolated a deletion allele of vav-1 . These animals arrest development during the first larval stage with difficulties in pharyngeal pumping. Specifically, the anterior muscles of the pharynx are paralyzed and the posterior muscle quivers asymmetrically as these animals attempt to feed. Using the myo-2 promoter, which drives expression in the pharyngeal muscle cells, we have been unable to rescue the vav-1 pharyngeal defects. However, when we use the pha-4 promoter, which drives expression in all pharyngeal cells, we can rescue the pharyngeal defects that arise in vav-1 mutants. Experiments are underway to find the specific cells where vav-1 is required for normal pharyngeal muscle contraction. When pharyngeal function is restored in vav-1 mutants, they are viable and can be maintained as homozygous mutants. This has enabled us to observe several other defects that arise in other tissues that are lacking vav-1 . These pharyngeal rescued animals have a reduced brood size and show defects in the timing of the defecation motor program. The brood size observed in these animals is about a third of what is observed for wild type animals. This defect is not the result of an egg-laying defect but it is the result of abnormal gonadal sheath cell/spermatheca contractions. In these animals, the contractions required for the normal signaling events to occur during ovulation appear irregular and several defects are observed in oocyte maturation and ovulation. For example, the ovulation of immature oocytes is observed, along with premature constriction of the spermatheca, which severs the oocyte in two, as well as the over extension of the spermatheca around adjacent oocytes. Finally, defecation in C. elegans consists of three sequential motor steps: posterior body wall muscle contraction, anterior body wall muscle contraction and expulsion. This motor program occurs approximately every 50s. In pharyngeal rescued vav-1 mutants, the timing of the defecation motor program is erratic and extended (average cycle is 75s). In conclusion, these data suggest that vav-1 functions in regulating rhythmic contractions in C. elegans .

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