Discovery of Ric-8 proteins: The Caenorhabditis elegans RIC-8 gene and a homologous mouse gene that was later termed Ric-8A (or a synembryn) were discovered by Miller and Rand using a genetic screen to obtain C. elegans mutants that were resistant to the inhibitor of cholinesterase, aldicarb (Miller et al. 1996). Aldicarb treatment of wild-type worms leads to neurotoxic accumulation of postsynaptic acetylcholine and subsequent death. Ric mutants lived in the presence of aldicarb because they contained gene defects that restored normal acetylcholine levels, primarily by decreasing neurotransmitter secretion or release. Through epistasis analyses, the gene complementing the ric-8 mutant allele was predicted to elicit action upstream of or parallel to the gene encoding G protein α q in a diacylglycerol-dependent synaptic-vesicle-priming pathway (Miller et al. 2000a). Miller and Rand...
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