Regulatory function of sympathetic innervation on the endo/lysosomal trafficking of acetylcholine receptor

Regulation of membrane receptors involves management of endocytosis. At the neuromuscular junction, the synapse between skeletal muscle and motoneuron, proper density of the major receptor, the acetylcholine receptor, is of utmost importance for sustaining life in context of mobility. Recent work has revealed innervation of NMJs by sympathetic neurons and destruction of them had morphological and functional consequences, suggesting influence on endocytosis. To investigate the pathways and proteins that are relevant for acetylcholine receptor turnover and affected by sympathetic signaling, proteomes of mouse hindlimb muscles from sympathectomized and saline-treated control muscles were compared. Using proteomic, Western blot, and immunofluorescence analysis in chemically sympathectomized mouse hindlimb muscles, the cause of these consequences were aimed to analyzed. This revealed extensive regulation of the proteome by the sympathetic nervous system and a possible regulatory function of the endo/lysosomal and autophagic pathway by sympathetic neuronal input. This finding might provide a new explanation to the observed benefit of sympathicomimetic treatment in several congenital myasthenic syndromes.

膜受体的调控涉及内吞作用（endocytosis）的调控。在神经肌肉接头（neuromuscular junction, NMJ）——即骨骼肌与运动神经元之间的突触——中，主要受体乙酰胆碱受体（acetylcholine receptor）的正常密度，对维持机体运动相关的生命功能至关重要。近期研究发现交感神经元可支配神经肌肉接头，破坏该神经支配会引发形态与功能层面的异常后果，提示交感神经元对内吞作用存在调控作用。为探究与乙酰胆碱受体更新相关且受交感信号调控的通路与蛋白质，研究人员对接受交感神经切除术的小鼠后肢肌肉与生理盐水处理的对照肌肉的蛋白质组进行了对比分析。本研究通过对化学法诱导交感神经切除的小鼠后肢肌肉开展蛋白质组学、蛋白质免疫印迹(Western blot)及免疫荧光分析，旨在解析上述异常后果的成因。研究结果显示，交感神经系统可对蛋白质组产生广泛调控，且交感神经元输入可能通过内吞/溶酶体及自噬通路发挥调控功能。该发现可为临床观察到的拟交感神经治疗对若干先天性肌无力综合征的获益提供全新的解释视角。