We are interested in understanding how Goa regulates C. elegans behavior. To uncover genes downstream of
goa-1, including possible effectors, we mutagenized animals carrying an integrated transgene which contains constitutively activated
goa-1 under control of a heat shock promoter (syIs17). Upon heat shock these animals become increasingly lethargic and stop producing and laying eggs (Mendel et al., Science 267: 1652-1655 (1995)). We applied heat shock to the adult grandprogeny of mutagenized animals and screened for mutants which could still move, forage, eat and reproduce. Out of 21,000 haploid genomes screened so far, 21 suppressors were isolated which define 7 complementation groups. The Sag (suppressor of activated G protein) loci fall roughly into three phenotypic classes. Two loci (
sag-1 and
sag-2) display some hyperactivity and other phenotypes reminiscent of, but not identical to,
goa-1 loss of function mutants. Two loci (
sag-4 and
sag-6) are nearly wildtype in appearance and behavior. Finally, two loci (
sag-3 and
sag-7) are egg laying and copulation defective.
sag-5 animals have variable phenotypes and have not been further characterized at this time. The
sag-1 locus is defined by 13 independent mutations which map to the left arm of the X chromosome, between
unc-1 and
dpy-3. The two most severe mutants exhibit multiple phenotypes, including a skinny, starved appearance, some hyperactivity, constitutive egg laying, slow egg production, and defects in mating behavior, especially at the turning step. We are currently mapping
sag-1 more closely with the intention of cloning it. Besides
sag-1, one other locus is defined by more than one mutation. Three mutations define the
sag-4 locus, which resides on chromosome V between
unc-42 and
lin-25. All of the other suppressors are defined by one mutation each, indicating that we may still be far from saturation. We also isolated a double mutant that left tracks with extremely exaggerated sine waves. When separated, one of the mutations was Sag, X-linked, and failed to complement the
sag-1 reference allele. The other mutation, which resides on chromosome V, is not Sag but displays the exaggerated movement. Although this mutant leaves tracks with greater amplitude, it does not move significantly more rapidly than its syIs17 parent. In addition, while
sag-2 animals have several phenotypes in common with
goa-1 loss of function mutants including more rapid movement (Segalat et al., Science 267: 1648-1651 (1995)), the tracks they leave do not have a higher amplitude than wildtype, unlike
goa-1(lf) animals (op. cit.). Therefore these two mutants suggest that frequency and amplitude of C. elegans movement may be separately controlled.