A GENETIC SELECTION FOR CAENORHABDITIS-ELEGANS SYNAPTIC TRANSMISSION MUTANTS

We have isolated 165 Caenorhabditis elegans mutants, representing 21 g enes, that are resistant to inhibitors of cholinesterase (Ric mutants) , Since mutations in 20 of the genes appear not to affect acetylcholin e reception, we suggest that reduced acetylcholine release contributes to the Ric phenotype of most Ric mutants, Mutations in 15 of the gene s lead to defects in a gamma-aminobutyric acid-dependent behavior; the se genes are likely to encode proteins with general, rather than choli nergic-specific, roles in synaptic transmission. Ten of the genes have been cloned, Seven encode homologs of proteins that function in the s ynaptic vesicle cycle: two encode cholinergic-specific proteins, while five encode general presynaptic proteins. Two other Ric genes encode homologs of G-protein signaling molecules. Our assessment of synaptic function in Ric mutants, combined with the homologies of some Ric muta nts to presynaptic proteins, suggests that the analysis of Ric genes w ill continue to yield insights into the regulation and functioning of synapses.