Netrin and Frazzled Regulate Presynaptic Gap Junctions at a Drosophila Giant Synapse
Netrin and Frazzled Regulate Presynaptic Gap Junctions at a Drosophila Giant Synapse
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DOI：
10.1523/jneurosci.3183-13.2014
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发表时间：
2014-04
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影响因子：
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通讯作者：
Brian O. Orr;Melissa A Borgen;Phyllis M Caruccio;R. Murphey
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作者：
Brian O. Orr;Melissa A Borgen;Phyllis M Caruccio;R. Murphey
Netrin及其受体Frazzled通过调节突触前末梢缝隙连接的定位，决定了果蝇巨纤维系统（GFS）突触连接的强度。在Netrin突变动物中，巨大的中间神经元和"跳跃"运动神经元之间的突触耦合减弱，这两个神经元之间的染料耦合严重受损或缺失。在Netrin突变体显示出明显正常的突触解剖结构的情况下，一半的标本表现出生理缺陷的突触，并且巨纤维（GF）和运动神经元之间的染料偶联减少或消除，这表明在Netrin突变体中间隙连接被破坏。当我们用Shaking-B（ShakB）Innexin抗体检查差距连接时，突变GF的突触前末端中间隙连接显著减少或缺失。Frazzled功能丧失突变体在突触传递、染料偶联和间隙连接定位方面表现出类似的缺陷。这些数据首次表明Netrin和Frazzled调节突触前间隙连接的位置。
Netrin and its receptor, Frazzled, dictate the strength of synaptic connections in the giant fiber system (GFS) of Drosophila melanogaster by regulating gap junction localization in the presynaptic terminal. In Netrin mutant animals, the synaptic coupling between a giant interneuron and the “jump” motor neuron was weakened and dye coupling between these two neurons was severely compromised or absent. In cases in which Netrin mutants displayed apparently normal synaptic anatomy, half of the specimens exhibited physiologically defective synapses and dye coupling between the giant fiber (GF) and the motor neuron was reduced or eliminated, suggesting that gap junctions were disrupted in the Netrin mutants. When we examined the gap junctions with antibodies to Shaking-B (ShakB) Innexin, they were significantly decreased or absent in the presynaptic terminal of the mutant GF. Frazzled loss of function mutants exhibited similar defects in synaptic transmission, dye coupling, and gap junction localization. These data are the first to show that Netrin and Frazzled regulate the placement of gap junctions presynaptically at a synapse.