Drosophila neuroligin 2 is required presynaptically and postsynaptically for proper synaptic differentiation and synaptic transmission.
Drosophila neuroligin 2 is required presynaptically and postsynaptically for proper synaptic differentiation and synaptic transmission.
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果蝇神经素2在突触前和突触后需要进行适当的突触分化和突触传播。
DOI：
10.1523/jneurosci.1685-12.2012
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发表时间：
2012-11-07
期刊：
影响因子：
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通讯作者：
Bhat MA
中科院分区：
文献类型：
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作者：
Chen YC;Lin YQ;Banerjee S;Venken K;Li J;Ismat A;Chen K;Duraine L;Bellen HJ;Bhat MA
Neurexins和Neuroligins之间的跨突触粘附被认为是正确的突触组织和调节所必需的，并且几种人类Neuroligins中的突变已显示与自闭症谱系障碍（ASD）相关。在这里，我们报告果蝇神经连接素2（dnlg 2）突变体的产生和表型特征。dnlg 2的丢失导致减少的结数量、神经肌肉接头（NMJ）处的异常突触前和突触后发育以及受损的突触传递。在dnlg 2突变体中，诱发反应的幅度降低，而在NMJ的总活性区数与野生型相当，这表明释放概率降低。在超微结构上，dnlg 2突变体的突触前活动区数目/终扣面积和突触后密度面积均增加，而突触下网状结构（SSR）的体积减少。我们发现，无论是前和突触后表达的Dnlg 2是需要恢复突触的生长和功能的dnlg 2突变体。在dnlg 2突变体和野生型中Dnlg 2的突触后表达导致减少的终扣生长，而在野生型动物中突触前和突触后过表达导致突触过度生长。由于神经配蛋白已被证明与神经毒素结合，我们创造了双突变体。这些突变体是可行的，并显示出与dnlg 2和dnlg 3单突变体非常相似的表型。我们的研究结果提供了令人信服的证据表明，Dnlg 2功能前和突触后与Neurexin一起，以确定适当数量的终扣以及活跃区的数量和突触密度的大小在NMJ的发展。
Trans-synaptic adhesion between Neurexins and Neuroligins is thought to be required for proper synapse organization and modulation, and mutations in several human NEUROLIGINS have shown association with autism spectrum disorders (ASD). Here we report the generation and phenotypic characterization of Drosophila neuroligin 2 (dnlg2) mutants. Loss of dnlg2 results in reduced bouton numbers, aberrant pre- and post-synaptic development at neuromuscular junctions (NMJs), and impaired synaptic transmission. In dnlg2 mutants, the evoked responses are decreased in amplitude, whereas the total active zone numbers at the NMJ are comparable to wild type, suggesting a decrease in the release probability. Ultrastructurally, the presynaptic active zone number per bouton area and the postsynaptic density area are both increased in dnlg2 mutants, whereas the subsynaptic reticulum (SSR) is reduced in volume. We show that both pre- and post-synaptic expression of Dnlg2 is required to restore synaptic growth and function in dnlg2 mutants. Post-synaptic expression of Dnlg2 in dnlg2 mutants and wild type leads to reduced bouton growth whereas pre- and post-synaptic overexpression in wild type animals results in synaptic overgrowth. Since Neuroligins have been shown to bind to Neurexins, we created double mutants. These mutants are viable and display phenotypes that closely resemble those of dnlg2 and dnrx single mutants. Our results provide compelling evidence that Dnlg2 functions both pre- and post-synaptically together with Neurexin to determine the proper number of boutons as well as the number of active zones and size of synaptic densities during the development of NMJs.