Distinct Presynaptic and Postsynaptic Dismantling Processes of Drosophila Neuromuscular Junctions during Metamorphosis
Distinct Presynaptic and Postsynaptic Dismantling Processes of Drosophila Neuromuscular Junctions during Metamorphosis
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DOI：
10.1523/jneurosci.0410-10.2010
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发表时间：
2010-09-01
影响因子：
5.3
通讯作者：
Zhang, Yong Q.
中科院分区：
文献类型：
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作者：
Liu, Zhiwei;Chen, Yan;Zhang, Yong Q.
突触重塑是一个广泛和基本的过程，在发育和适应生理和/或环境变化的神经元回路的形成的基础。然而，突触重塑的机制知之甚少。果蝇幼虫神经肌肉接头处的突触在变态过程中经历了剧烈而广泛的重塑，以产生成体特异性突触。为了探索突触消除的分子和细胞过程，我们进行了共聚焦显微镜，实时成像，和电子显微镜（EM）的NMJ突触在果蝇的早期阶段的变态，其中选定的基因的表达被遗传改变。我们报告说，本地化的突触后支架蛋白光盘大（DLG）成为弥漫性的第一，然后无法检测到，作为幼虫肌肉进行组织溶解，而突触前囊泡聚集和逆行运输沿着轴突与丝状伪足样结构的形成同步沿着NMJ阐述和收缩的突触前质膜。电镜观察发现，在突触解体的早期，突触后突触下网状结构空泡化，并伴有Dlg的弥漫性定位。蜕皮激素是驱动变态的主要激素。通过表达显性负性形式的蜕皮激素受体阻断特异性突触前神经元的蜕皮激素信号传导延迟了突触前但不延迟突触后拆除。然而，抑制蜕皮激素信号，以及泛素化途径或细胞凋亡，特别是在突触后肌肉，逮捕突触前和突触后拆除。这些结果表明，突触前和突触后的拆除发生通过不同的机制，突触后侧起着指导作用的突触拆除。
Synapse remodeling is a widespread and fundamental process that underlies the formation of neuronal circuitry during development and in adaptation to physiological and/or environmental changes. However, the mechanisms of synapse remodeling are poorly understood. Synapses at the neuromuscular junction (NMJ) in Drosophila larvae undergo dramatic and extensive remodeling during metamorphosis to generate adult-specific synapses. To explore the molecular and cellular processes of synapse elimination, we performed confocal microscopy, live imaging, and electron microscopy (EM) of NMJ synapses during the early stages of metamorphosis in Drosophila in which the expressions of selected genes were genetically altered. We report that the localization of the postsynaptic scaffold protein Disc large (Dlg) becomes diffuse first and then undetectable, as larval muscles undergo histolysis, whereas presynaptic vesicles aggregate and are retrogradely transported along axons in synchrony with the formation of filopodia-like structures along NMJ elaborations and retraction of the presynaptic plasma membrane. EM revealed that the postsynaptic subsynaptic reticulum vacuolizes in the early stages of synapse dismantling concomitant with diffuse localization of Dlg. Ecdysone is the major hormone that drives metamorphosis. Blockade of the ecdysone signaling specifically in presynaptic neurons by expression of a dominant-negative form of ecdysone receptors delayed presynaptic but not postsynaptic dismantling. However, inhibition of ecdysone signaling, as well as ubiquitination pathway or apoptosis specifically in postsynaptic muscles, arrested both presynaptic and postsynaptic dismantling. These results demonstrate that presynaptic and postsynaptic dismantling takes place through different mechanisms and that the postsynaptic side plays an instructive role in synapse dismantling.