Analysis of adhesion molecules and basement membrane contributions to synaptic adhesion at the Drosophila embryonic NMJ.
Analysis of adhesion molecules and basement membrane contributions to synaptic adhesion at the Drosophila embryonic NMJ.
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粘附分子和基底膜对果蝇胚胎NMJ上突触粘附的贡献的分析。
DOI：
10.1371/journal.pone.0036339
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Prokop A
中科院分区：
文献类型：
--
作者：
Koper A;Schenck A;Prokop A
突触的形成和维持是健康和疾病中大脑功能的关键基础。这两个过程都被认为依赖于细胞黏附分子(CAM)。许多不同类型的CaM定位于突触，包括钙粘蛋白、原钙粘素、神经连接蛋白、神经尿素素、整合素和免疫球蛋白黏附蛋白，进一步的贡献来自细胞外基质及其受体。这些因素中的大多数已经通过动物模型的功能丧失分析进行了仔细的研究。然而，哪些黏附因子建立了跨越突触间隙的必要物理联系，并允许在体内接触部位组装突触机械，目前仍不清楚。为了研究这些关键问题，我们使用果蝇胚胎的神经肌肉接头(NMJ)作为遗传上可服从的突触模型。我们对缺乏不同类别的CaM的NMJ的超微结构分析显示，所有Neurexin、所有经典钙粘附素或所有谷氨酸受体的丢失，以及它们之间的组合或伴层粘连蛋白缺乏，都无法揭示结构表型。这些结果与一种观点是一致的，即这些凸轮可能在这个模型突触中没有结构性作用。然而，我们认为它们更有可能在冗余或缓冲良好的环境中运行。我们提出了一个基于多适配器原理的模型来解释这一现象。此外，我们报告了一种新的不依赖于CAM的粘连机制，涉及覆盖神经肌肉终末的基底膜(BM)。因此，当BM与细胞表面的附着因去除层粘连蛋白A而受损时，或当BM因失去IV型胶原而失去结构完整性时，运动神经元终末显示出强烈的部分连接分离。我们得出结论，BMS对于将胚胎运动神经元终末连接到肌肉表面是必不可少的，为它们的粘连提供了不依赖于CAM的结构支持。因此，未来对果蝇这些突触连接的发育研究需要考虑除CAM依赖的黏附外，BM依赖的机制所做出的重要贡献。
Synapse formation and maintenance crucially underlie brain function in health and disease. Both processes are believed to depend on cell adhesion molecules (CAMs). Many different classes of CAMs localise to synapses, including cadherins, protocadherins, neuroligins, neurexins, integrins, and immunoglobulin adhesion proteins, and further contributions come from the extracellular matrix and its receptors. Most of these factors have been scrutinised by loss-of-function analyses in animal models. However, which adhesion factors establish the essential physical links across synaptic clefts and allow the assembly of synaptic machineries at the contact site in vivo is still unclear. To investigate these key questions, we have used the neuromuscular junction (NMJ) of Drosophila embryos as a genetically amenable model synapse. Our ultrastructural analyses of NMJs lacking different classes of CAMs revealed that loss of all neurexins, all classical cadherins or all glutamate receptors, as well as combinations between these or with a Laminin deficiency, failed to reveal structural phenotypes. These results are compatible with a view that these CAMs might have no structural role at this model synapse. However, we consider it far more likely that they operate in a redundant or well buffered context. We propose a model based on a multi-adaptor principle to explain this phenomenon. Furthermore, we report a new CAM-independent adhesion mechanism that involves the basement membranes (BM) covering neuromuscular terminals. Thus, motorneuronal terminals show strong partial detachment of the junction when BM-to-cell surface attachment is impaired by removing Laminin A, or when BMs lose their structural integrity upon loss of type IV collagens. We conclude that BMs are essential to tie embryonic motorneuronal terminals to the muscle surface, lending CAM-independent structural support to their adhesion. Therefore, future developmental studies of these synaptic junctions in Drosophila need to consider the important contribution made by BM-dependent mechanisms, in addition to CAM-dependent adhesion.
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