A genetic selection for Caenorhabditis elegans synaptic transmission mutants.
We have isolated 165 Caenorhabditis elegans mutants, representing 21 genes, that are resistant to inhibitors of cholinesterase (Ric mutants). Since mutations in 20 of the genes appear not to affect acetylcholine reception, we suggest that reduced acetylcholine release contributes to the Ric phenotype of most Ric mutants. Mutations in 15 of the genes lead to defects in a gamma-aminobutyric acid-dependent behavior; these genes are likely to encode proteins with general, rather than cholinergic-specific, roles in synaptic transmission. Ten of the genes have been cloned. Seven encode homologs of proteins that function in the synaptic 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 mutants to presynaptic proteins, suggests that the analysis of Ric genes will continue to yield insights into the regulation and functioning of synapses.
Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
K G
KG
Miller
A
A
Alfonso
M
M
Nguyen
J A
JA
Crowell
C D
CD
Johnson
J B
JB
Rand
D000109:Acetylcholine / Q000378:metabolism; D000448:Aldicarb / Q000494:pharmacology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D015801:Helminth Proteins / Q000235:genetics*; D007978:Levamisole / Q000494:pharmacology; D016296:Mutagenesis; D010641:Phenotype; D011950:Receptors, Cholinergic / Q000378:metabolism; D015398:Signal Transduction; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002800:Cholinesterase Inhibitors; D015801:Helminth Proteins; D011950:Receptors, Cholinergic; D007978:Levamisole; D005680:gamma-Aminobutyric Acid; D000448:Aldicarb; D000109:Acetylcholine