aex-3 encodes a novel regulator of presynaptic activity in C-elegans
aex-3 encodes a novel regulator of presynaptic activity in C-elegans
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DOI：
10.1016/s0896-6273(00)80302-5
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发表时间：
1997-04-01
期刊：
影响因子：
16.2
通讯作者：
Thomas, JH
中科院分区：
文献类型：
--
作者：
Iwasaki, K;Staunton, J;Thomas, JH
线虫AEX-3突变导致多效性行为缺陷，提示突触传递减少。AEX-3突变与UNC-31和UNC-突变也显示出强烈的遗传相互作用，这两个基因与突触传递有关。生理学和药理学研究表明，AEX-3缺陷是突触前的。在AEX-3突变体中，突触小泡相关的RAB-3蛋白异常聚集在神经元细胞体中，并在富含突触的轴突中减少。这种定位缺陷是RAB-3特有的，因为其他突触蛋白在AEX-3突变体中正常定位。AEX-3编码1409个氨基酸的蛋白质，与未知功能的人类蛋白质Denn有很强的同源性。在线虫中，AEX-3在所有或几乎所有神经元中都有表达。这些结果表明，AEX-3是一种新的突触前活动调节剂，它与RAB-3相互作用，调节突触小泡的释放。
C. elegans aex-3 mutations cause pleiotropic behavioral defects that are suggestive of reduced synaptic transmission. aex-3 mutations also show strong genetic interactions with mutations in unc-31 and unc-64, two other genes implicated in synaptic transmission. Physiological and pharmacological studies indicate that aex-3 defects are presynaptic. In aex-3 mutants, the synaptic vesicle-associated RAB-3 protein aberrantly accumulates in neuronal cell bodies and is reduced in synapse-rich axons. This localization defect is specific to RAB-3, since other synaptic proteins are localized normally in aex-3 mutants. aex-3 encodes a 1409 amino acid protein with strong homology to DENN, a human protein of unknown function. In C. elegans, aex-3 is expressed in all or nearly all neurons. These results suggest that AEX-3 is a novel regulator of presynaptic activity that interacts with RAB-3 to regulate synaptic vesicle release.