Recent studies describe a network of signaling proteins centered around GOA-1 (Goa) and EGL-30 (Gqa) that regulates neurotransmitter secretion in C. elegans by controlling the production and consumption of diacylglycerol (DAG). We sought other components of the Goa-Gqa signaling network by screening for aldicarb resistant mutants with phenotypes similar to
egl-30 (Gqa) mutants. In so doing we identified
ric-8, which encodes a novel protein named RIC-8 (synembryn). Through cDNA analysis we show that RIC-8 is conserved in vertebrates. Through immunostaining we show that RIC-8 is concentrated in the cytoplasm of neurons. Exogenous application of phorbol esters or loss of DGK-1 (diacylglycerol kinase) rescues
ric-8 mutant phenotypes. A genetic analysis suggests that RIC-8 functions upstream of EGL-30 (Gqa), or in a parallel intersecting pathway. Both
ric-8 and
goa-1 reduction of function mutants also exhibit partial embryonic lethality. Furthermore, the embryonic lethality of
ric-8 mutants is enhanced to 95-100% by a 50% reduction in maternal
goa-1 gene dosage. In a separate study we investigated the roles of RIC-8 and GOA-1 in early embryos (pre 8-cell stage) and found that
goa-1 and
ric-8 mutant embryos exhibit defects in the movements of centrosomes. Comparing the roles of RIC-8 and GOA-1 in the nervous system and the embryo reveals potentially informative differences between the two pathways. First, EGL-30 (Gqa) does not appear to play a role in the embryonic pathway. Second, in the embryonic pathway, reduction of function mutations in
goa-1 and
ric-8 lead to similar phenotypes that are enhanced in
goa-1;
ric-8 double mutants, whereas in the adult neuronal pathway the same
goa-1 and
ric-8 mutants have opposite phenotypes and suppress each other. Based on these findings, we propose that RIC-8 is required, directly or indirectly, for proper activation of G proteins in the early embryo and in the nervous system.