Richards S, Hillman T, Stern M
Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77251, USA.
Genetics. 1996 Apr;142(4):1215-23. doi: 10.1093/genetics/142.4.1215.
We describe the identification of a gene called pushover (push), which affects both behavior and synaptic transmission at the neuromuscular junction. Adults carrying either of two mutations in push exhibit sluggishness, uncoordination, a defective escape response, and male sterility. Larvae defective in push exhibit increased release of transmitter at the neuromuscular junction. In particular, the frequency of spontaneous transmitter release and the amount of transmitter release evoked by nerve stimulation are each increased two- to threefold in push mutants at the lowest external [Ca2+] tested (0.15 mM). Furthermore, these mutants are more sensitive than wild type to application of the potassium channel-blocking drug quinidine: following quinidine application, push mutants, but not wild-type, display repetitive firing of the motor axon, leading to repetitive muscle postsynaptic potentials. The push gene thus might affect both neuronal excitability and the transmitter release process. Complementation tests and recombinational mapping suggest that the push mutations are allelic to a previously identified P-element-induced mutation, which also causes behavioral abnormalities and male sterility.
我们描述了一个名为“推倒”（push）基因的鉴定过程，该基因影响神经肌肉接头处的行为和突触传递。携带push基因两种突变之一的成虫表现出行动迟缓、不协调、逃避反应缺陷以及雄性不育。push基因有缺陷的幼虫在神经肌肉接头处表现出递质释放增加。特别是，在测试的最低外部[Ca2+]（0.15 mM）条件下，push突变体中自发递质释放的频率和神经刺激诱发的递质释放量均增加了两到三倍。此外，这些突变体比野生型对钾通道阻断药物奎尼丁的应用更敏感：应用奎尼丁后，push突变体而非野生型会出现运动轴突的重复放电，导致肌肉突触后电位重复出现。因此，push基因可能同时影响神经元兴奋性和递质释放过程。互补试验和重组定位表明，push突变与先前鉴定的P元件诱导突变等位，该突变也会导致行为异常和雄性不育。
