Miller K G, Alfonso A, Nguyen M, Crowell J A, Johnson C D, Rand J B
Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12593-8. doi: 10.1073/pnas.93.22.12593.
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.
我们分离出了165个秀丽隐杆线虫突变体，它们代表21个基因，对胆碱酯酶抑制剂具有抗性（Ric突变体）。由于其中20个基因的突变似乎不影响乙酰胆碱的接收，我们认为乙酰胆碱释放减少是大多数Ric突变体的Ric表型的原因。其中15个基因的突变导致γ-氨基丁酸依赖性行为出现缺陷；这些基因可能编码在突触传递中具有一般作用而非胆碱能特异性作用的蛋白质。已克隆出其中10个基因。7个基因编码在突触小泡循环中起作用的蛋白质的同源物：2个编码胆碱能特异性蛋白质，而5个编码一般的突触前蛋白质。另外两个Ric基因编码G蛋白信号分子的同源物。我们对Ric突变体突触功能的评估，结合一些Ric突变体与突触前蛋白质的同源性，表明对Ric基因的分析将继续为突触的调节和功能提供深入见解。
