Morphological and functional effects of altered cysteine string protein at the Drosophila larval neuromuscular junction
Morphological and functional effects of altered cysteine string protein at the Drosophila larval neuromuscular junction
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DOI：
10.1002/syn.20335
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发表时间：
2007-01-01
期刊：
影响因子：
2.3
通讯作者：
Atwood, Harold L.
中科院分区：
文献类型：
--
作者：
Dawson-Scully, Ken;Lin, Yongqi;Atwood, Harold L.
突触囊泡相关的半胱氨酸串蛋白（CSP）是果蝇神经肌肉接头（NMJ）神经递质释放的关键，其中约4%缺乏CSP的突变果蝇存活至成年后表现出痉挛性跳跃和颤抖，温度敏感性麻痹和过早死亡。以前，已经表明CSP也是果蝇和小鼠神经末梢生长和预防神经变性所必需的。在果蝇幼虫csp无效突变体NMJ，从肌肉的细胞内记录显示，诱发释放在室温下显着减少。然而，目前还不清楚是否诱发释放的减少可能是由于突触扣的损失，突触的损失，以及小泡运输到突触的改变。为了解决这些问题，我们已经研究了突触结构和功能的csp无效突变NMJ在单扣的水平。CSP无效突变成比例地减少了支配幼虫肌肉6和7的两个运动神经元（1S和1B）的突触结的数量，而每个结的突触数量保持正常。然而，从单个突触终扣的局灶性记录表明，神经诱发的神经递质释放也受损，在1s和1b终扣。此外，我们的超微结构分析表明，低刺激频率下诱发释放的减少并不是由于突触的丧失或突触处停靠囊泡的改变。总之，这些数据表明，CSP促进突触生长和诱发的神经递质释放的机械独立的信号通路。
The synaptic vesicle-associated cysteine string protein (CSP) is critical for neurotransmitter release at the neuromuscular junction (NMJ) of Drosophila, where the similar to 4% of mutant flies lacking CSP that survive to adulthood exhibit spastic jumping and shaking, temperature-sensitive paralysis, and premature death. Previously, it has been shown that CSP is also required for nerve terminal growth and the prevention of neurodegeneration in Drosophila and mice. At larval csp null mutant NMJs of Drosophila, intracellular recordings from the muscle showed that evoked release is significantly reduced at room temperature. However, it remained unclear whether the reduction in evoked release might be due to a loss of synaptic boutons, loss of synapses, and alterations in trafficking of vesicles to synapses. To resolve these issues, we have examined synaptic structure and function of csp null mutant NMJs at the level of single boutons. csp null mutations proportionally reduce the number of synaptic boutons of both motor neurons (1s and 1b) innervating larval muscles 6 and 7, while the number of synapses per bouton remains normal. However, focal recordings from individual synaptic boutons show that nerve-evoked neurotransmitter release is also impaired in both 1s and 1b boutons. Further, our ultrastructural analyses show that the reduction in evoked release at low stimulation frequencies is not due to a loss of synapses or to alterations in docked vesicles at synapses. Together, these data suggest that CSP promotes synaptic growth and evoked neurotransmitter release by mechanistically independent signaling pathways.