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Drosophila enabled promotes synapse morphogenesis and regulates active zone form and function.
Neural Development ( IF 4.0 ) Pub Date : 2020-03-17 , DOI: 10.1186/s13064-020-00141-x
Elizabeth M McNeill 1 , Cheryl Thompson 2 , Brett Berke 3 , Vivian T Chou 2 , Jannette Rusch 2 , April Duckworth 2 , Jamin DeProto 2 , Alicia Taylor 1, 2 , Julie Gates 4 , Frank Gertler 5 , Haig Keshishian 3 , David Van Vactor 2
Affiliation  

BACKGROUND Recent studies of synapse form and function highlight the importance of the actin cytoskeleton in regulating multiple aspects of morphogenesis, neurotransmission, and neural plasticity. The conserved actin-associated protein Enabled (Ena) is known to regulate development of the Drosophila larval neuromuscular junction through a postsynaptic mechanism. However, the functions and regulation of Ena within the presynaptic terminal has not been determined. METHODS Here, we use a conditional genetic approach to address a presynaptic role for Ena on presynaptic morphology and ultrastructure, and also examine the pathway in which Ena functions through epistasis experiments. RESULTS We find that Ena is required to promote the morphogenesis of presynaptic boutons and branches, in contrast to its inhibitory role in muscle. Moreover, while postsynaptic Ena is regulated by microRNA-mediated mechanisms, presynaptic Ena relays the output of the highly conserved receptor protein tyrosine phosphatase Dlar and associated proteins including the heparan sulfate proteoglycan Syndecan, and the non-receptor Abelson tyrosine kinase to regulate addition of presynaptic varicosities. Interestingly, Ena also influences active zones, where it restricts active zone size, regulates the recruitment of synaptic vesicles, and controls the amplitude and frequency of spontaneous glutamate release. CONCLUSION We thus show that Ena, under control of the Dlar pathway, is required for presynaptic terminal morphogenesis and bouton addition and that Ena has active zone and neurotransmission phenotypes. Notably, in contrast to Dlar, Ena appears to integrate multiple pathways that regulate synapse form and function.

中文翻译:

启用的果蝇促进突触形态发生并调节活动区的形式和功能。

背景突触形式和功能的最新研究强调了肌动蛋白细胞骨架在调节形态发生、神经传递和神经可塑性的多个方面的重要性。已知保守的肌动蛋白相关蛋白 Enabled (Ena) 通过突触后机制调节果蝇幼虫神经肌肉接头的发育。然而,Ena 在突触前末梢的功能和调节尚未确定。方法在这里,我们使用条件遗传方法来解决 Ena 对突触前形态和超微结构的突触前作用,并通过上位性实验检查 Ena 发挥作用的途径。结果 我们发现 Ena 需要促进突触前 boutons 和分支的形态发生,与其在肌肉中的抑制作用相反。此外,虽然突触后 Ena 受 microRNA 介导的机制调节,但突触前 Ena 传递高度保守的受体蛋白酪氨酸磷酸酶 Dlar 和相关蛋白(包括硫酸乙酰肝素蛋白聚糖 Syndecan 和非受体 Abelson 酪氨酸激酶)的输出,以调节突触前静脉曲张的增加。有趣的是,Ena 还影响活动区,在那里它限制活动区的大小,调节突触小泡的募集,并控制自发谷氨酸释放的幅度和频率。结论因此,我们表明 Ena 在 Dlar 通路的控制下,是突触前终末形态发生和 bouton 添加所必需的,并且 Ena 具有活性区和神经传递表型。值得注意的是,与 Dlar 相比,
更新日期:2020-04-22
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