Abstract：
Neuromuscular junctions transmit signals from the nervous system to skeletal muscles, triggering their contraction, and their proper organization is essential for breathing and voluntary movements. αDystrobrevin-1 is a cytoplasmic component of the dystrophin-glycoprotein complex and has pivotal functions in regulating the integrity of muscle fibers and neuromuscular junctions. Previous studies identified that αDystrobrevin-1 functions in the organization of the neuromuscular junction and that its phosphorylation in the C-terminus is required in this process. Our proteomic screen identified several putative αDystrobrevin-1 interactors recruited to the Y730 site in phosphorylated and unphosphorylated states. Amongst various actin-modulating proteins, we identified the Arp2/3 complex regulator cortactin. We showed that similarly to αDystrobrevin-1, cortactin is strongly enriched at the neuromuscular postsynaptic machinery and obtained results suggesting that these two proteins interact in cell homogenates and at the neuromuscular junctions. Analysis of synaptic morphology in cortactin knockout mice showed abnormalities in the slow-twitching soleus muscle and not in the fast-twitching tibialis anterior. However, muscle strength examination did not reveal apparent deficits in knockout animals.
摘要：
神经肌肉接头将信号从神经系统传输到骨骼肌，引发他们的收缩，它们的适当组织对于呼吸和自愿运动至关重要。αDystrobrevin-1是肌营养不良蛋白-糖蛋白复合物的细胞质成分，在调节肌纤维和神经肌肉接头的完整性方面具有关键作用。先前的研究确定αDystrobrevin-1在神经肌肉接头的组织中起作用，并且在该过程中需要其在C末端的磷酸化。我们的蛋白质组学筛选鉴定了以磷酸化和非磷酸化状态募集到Y730位点的几种推定的αDystrobrevin-1相互作用物。在各种肌动蛋白调节蛋白中，我们鉴定了Arp2/3复合调节因子cortactin。我们表明，与αDystrobrevin-1类似，皮质肌动蛋白在神经肌肉突触后机制中强烈富集，并获得的结果表明这两种蛋白质在细胞匀浆和神经肌肉接头处相互作用。对皮质肌动蛋白敲除小鼠的突触形态的分析显示，缓慢抽搐的比目鱼肌异常，而不是快速抽搐的胫骨前肌异常。然而,肌肉力量检查没有发现基因敲除动物的明显缺陷。
