Recent studies have demonstrated that neuromuscular junctions are co-innervated by sympathetic neurons. This co-innervation has been shown to be crucial for neuromuscular junction morphology and functional maintenance. To improve our understanding of how sympathetic innervation affects nerve–muscle synapse homeostasis, we here used in vivo imaging, proteomic, biochemical, and microscopic approaches to compare normal and sympathectomized mouse hindlimb muscles. Live confocal microscopy revealed reduced fiber diameters, enhanced acetylcholine receptor turnover, and increased amounts of endo/lysosomal acetylcholine-receptor-bearing vesicles. Proteomics analysis of sympathectomized skeletal muscles showed that besides massive changes in mitochondrial, sarcomeric, and ribosomal proteins, the relative abundance of vesicular trafficking markers was affected by sympathectomy. Immunofluorescence and Western blot approaches corroborated these findings and, in addition, suggested local upregulation and enrichment of endo/lysosomal progression and autophagy markers, Rab 7 and p62, at the sarcomeric regions of muscle fibers and neuromuscular junctions. In summary, these data give novel insights into the relevance of sympathetic innervation for the homeostasis of muscle and neuromuscular junctions. They are consistent with an upregulation of endocytic and autophagic trafficking at the whole muscle level and at the neuromuscular junction.

最近的研究表明，交感神经元共同神经支配神经肌肉连接。已证明这种共支配对神经肌肉接头形态和功能维持至关重要。为了增进我们对交感神经支配如何影响神经-肌肉突触稳态的认识，我们在这里使用体内成像，蛋白质组学，生化和显微镜方法来比较正常和经交感神经切除的小鼠后肢肌肉。实时共聚焦显微镜显示纤维直径减少，乙酰胆碱受体代谢增加，内含/溶酶体乙酰胆碱受体的囊泡数量增加。交感神经切除的骨骼肌的蛋白质组学分析表明，除了线粒体，肌节蛋白和核糖体蛋白的大量变化外，交感神经切除术还影响了水泡运输标志物的相对丰度。免疫荧光和蛋白质印迹方法证实了这些发现，此外，还表明在肌纤维和神经肌肉接头的肌节区域局部上调和富集了内吞/溶酶体进展和自噬标记Rab 7和p62。总之，这些数据为交感神经支配与肌肉和神经肌肉接头的动态平衡的相关性提供了新颖的见解。它们与在整个肌肉水平和在神经肌肉接头处的内吞和自噬运输的上调相一致。