Differential muscle‐driven synaptic remodeling in the neuromuscular junction after denervation
Differential muscle‐driven synaptic remodeling in the neuromuscular junction after denervation
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去神经后神经肌肉接头的差异性肌肉驱动突触重塑
DOI：
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发表时间：
2010
影响因子：
3.4
通讯作者：
V. Witzemann
中科院分区：
文献类型：
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作者：
P. Yampolsky;Pier Giorgio Pacifici;V. Witzemann
我们使用表达绿色荧光蛋白（GFP）标记的胚胎型乙酰胆碱受体的敲入小鼠来研究快缩和慢缩肌纤维去神经支配的突触后反应，并观察新合成的GFP标记的胚胎型受体整合到成年突触中。胚胎型受体瞬时表达并整合到失神经终板中。它们以定向的方式取代突触性成人型受体，从终板的外围开始并进行到其中心区域。胚胎型受体表达在转录控制方面的进展是一种短暂的短期激活机制。GFP标记受体表达水平的不太明显的增加揭示了整合和降解过程中的差异变化，这些过程构成了突触受体库的动态平衡。因此，我们能够模拟神经肌肉终板的总受体负荷的变化，作为可用受体的丰度和终板的初始受体负荷的函数。
We used knock‐in mice that express green fluorescent protein (GFP)‐labeled embryonic‐type acetylcholine receptors to investigate postsynaptic responses to denervation of fast‐twitch and slow‐twitch muscle fibers, and to visualize the integration of newly synthesized GFP‐labeled embryonic‐type receptors into adult synapses. The embryonic‐type receptors are transiently expressed and incorporated into the denervated endplates. They replaced synaptic adult‐type receptors in a directed fashion, starting from the endplate’s periphery and proceeding to its central regions. The progress of embryonic‐type receptor expression with respect to transcriptional control is a transient, short‐term activation mechanism. The less pronounced increase in the expression levels of the GFP‐labeled receptors revealed a differential shift in the integration and degradation processes that constitute the dynamic equilibrium of the synaptic receptor pool. Therefore, we were able to model the changes in the total receptor load of the neuromuscular endplate following denervation as a function of the abundance of available receptors and the initial receptor load of the endplate.