Worms that lack the gene
goa-1, which encodes the alpha subunit of the heterotrimeric G protein Go, are small, have few progeny, and are hyperactive for locomotion, foraging, and egg laying behaviors. The hyperactivity of
goa-1 mutants fits in well with the data from vertebrates, in which Go has been shown to inhibit neural activity. We reasoned that mutations that decrease neural activity may suppress defects in
goa-1. We examined doubles between
goa-1 and mutants in the calcium channel genes
egl-19,
unc-36, and
unc-2, as Go inhibits calcium channels in vertebrates. The behavioral phenotypes of both mutants were partially rescued in these doubles. The animals were not hyper, but ranged from slow (
unc-36) to almost wild type (
egl-19).Surprisingly, when we quantitated the broods of the double mutants, we found that mutations in the two calcium channel genes which encode
a1 subunits,
unc-2 and
egl-19, partially suppress the brood size defects of
goa-1 null mutants, raising the average brood size from 36 to 70. We have also initiated a direct screen for suppressors of the infertility defect (Cardozo and Kaplan). Mike Finney, when originally working on
n363, performed such a screen and isolated an allele of
unc-31 that suppresses these defects. David Livingston and John White cloned
unc-31, which is homologous to
p145, a protein involved in synaptic release. Doubles with the gene
unc-64, which encodes a syntaxin homologue, are also suppressed for brood size. So mutations that reduce synaptic release, often the end result of neural activity, also suppress
goa-1 mutations. In both cases (exocytosis and calcium channel mutants) suppression can be explained by either of two models. The first is that Go directly regulates neurotransmitter release and calcium channels both cases are supported by data from other systems. In the absence of Go, there is too much calcium and/or neurotransmitter release, and defects in the appropriate genes bring the amount of calcium or release closer to wild type levels. The second is that a lack of Go leads to hyperexcited cells by raising the resting membrane potential, and that this general hyperexcitability is suppressed by mutations that generally reduce excitability, such as calcium channel mutations. We hope to distinguish between these models using electrophysiological techniques.