Neuron-type specific functions of DNT1, DNT2 and Spz at the Drosophila neuromuscular junction.
Neuron-type specific functions of DNT1, DNT2 and Spz at the Drosophila neuromuscular junction.
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DOI：
10.1371/journal.pone.0075902
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hidalgo A
中科院分区：
文献类型：
--
作者：
Sutcliffe B;Forero MG;Zhu B;Robinson IM;Hidalgo A
在果蝇的神经肌肉接头（NMJ）的突触可塑性的逆行生长因子调节长期以来一直被预测，但他们的发现一直很少。在脊椎动物中，这种由肌肉产生的逆行因子包括GDNF和神经营养因子（NT：NGF、BDNF、NT 3和NT 4）。NT超家族成员已被确定在整个无脊椎动物，但到目前为止，没有功能在体内分析已在NMJ在无脊椎动物进行。果蝇的NT蛋白家族由DNT 1、DNT 2和Spätzle（Spz）组成，相对于哺乳动物NT具有序列、结构和功能保守性。在这里，我们调查的功能果蝇NT（DNT）在幼虫NMJ。所有三种DNT都在幼虫体壁肌肉中表达，运动神经元的靶点。DNT在神经元中的过表达，或Spz受体Toll 10b的活化形式，仅在神经元中，挽救了spz 2和DNT 1 41、DNT 2 e03444双突变体的半致死性，表明神经元中的逆行功能。在spz 2突变体、DNT 1 41、DNT 2 e03444双突变体中，当DNT过表达时，NMJ大小和终扣数目增加。终扣形态异常。spz和DNT 1、DNT 2的突变导致每个终扣的活性区数量减少，并且每个末端的活性区密度减少。DNT功能的改变诱导了鬼结和突触碎片。spz 2突变体和DNT 1 41、DNT 2 e03444双突变体的诱发连接电位正常，但spz 2突变体的自发事件频率和幅度降低，提示神经传递缺陷。我们的数据表明，DNT产生于肌肉中，并且是神经元突触发生所需的。DNT功能和突触形成的改变最有可能诱导NMJ可塑性，导致稳态调整，增加末端大小，恢复整体突触传递。数据表明，Spz在肌肉4 NMJ处具有神经元类型特异性，而DNT 1和DNT 2在肌肉6，7 NMJ处一起起作用。
Retrograde growth factors regulating synaptic plasticity at the neuromuscular junction (NMJ) in Drosophila have long been predicted but their discovery has been scarce. In vertebrates, such retrograde factors produced by the muscle include GDNF and the neurotrophins (NT: NGF, BDNF, NT3 and NT4). NT superfamily members have been identified throughout the invertebrates, but so far no functional in vivo analysis has been carried out at the NMJ in invertebrates. The NT family of proteins in Drosophila is formed of DNT1, DNT2 and Spätzle (Spz), with sequence, structural and functional conservation relative to mammalian NTs. Here, we investigate the functions of Drosophila NTs (DNTs) at the larval NMJ. All three DNTs are expressed in larval body wall muscles, targets for motor-neurons. Over-expression of DNTs in neurons, or the activated form of the Spz receptor, Toll 10b, in neurons only, rescued the semi-lethality of spz 2 and DNT1 41 , DNT2 e03444 double mutants, indicating retrograde functions in neurons. In spz 2 mutants, DNT1 41 , DNT2 e03444 double mutants, and upon over-expression of the DNTs, NMJ size and bouton number increased. Boutons were morphologically abnormal. Mutations in spz and DNT1,DNT2 resulted in decreased number of active zones per bouton and decreased active zone density per terminal. Alterations in DNT function induced ghost boutons and synaptic debris. Evoked junction potentials were normal in spz 2 mutants and DNT1 41 , DNT2 e03444 double mutants, but frequency and amplitude of spontaneous events were reduced in spz 2 mutants suggesting defective neurotransmission. Our data indicate that DNTs are produced in muscle and are required in neurons for synaptogenesis. Most likely alterations in DNT function and synapse formation induce NMJ plasticity leading to homeostatic adjustments that increase terminal size restoring overall synaptic transmission. Data suggest that Spz functions with neuron-type specificity at the muscle 4 NMJ, and DNT1 and DNT2 function together at the muscles 6,7 NMJ.
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影响因子：
2.7
作者：
Halfon, MS;Keshishian, H
通讯作者：
Keshishian, H
影响因子：
64.8
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HALFON, MS;HASHIMOTO, C;KESHISHIAN, H
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