Schwarte Russell C, Godfrey Earl W
Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23501, USA.
Dev Biol. 2004 Sep 15;273(2):276-84. doi: 10.1016/j.ydbio.2004.06.003.
Agrin, a synapse-organizing protein externalized by motor axons at the neuromuscular junction (NMJ), initiates a signaling cascade in muscle cells leading to aggregation of postsynaptic proteins, including acetylcholine receptors (AChRs). We examined whether nitric oxide synthase (NOS) activity is required for agrin-induced aggregation of postsynaptic AChRs at the embryonic NMJ in vivo and in cultured muscle cells. Inhibition of NOS reduced AChR aggregation at embryonic Xenopus NMJs by 50-90%, whereas overexpression of NOS increased AChR aggregate area 2- to 3-fold at these synapses. NOS inhibitors completely blocked agrin-induced AChR aggregation in cultured embryonic muscle cells. Application of NO donors to muscle cells induced AChR clustering in the absence of agrin. Our results indicate that NOS activity is necessary for postsynaptic differentiation of embryonic NMJs and that NOS is a likely participant in the agrin-MuSK signaling pathway of skeletal muscle cells.
聚集蛋白是一种在神经肌肉接头（NMJ）处由运动轴突外化的突触组织蛋白，它在肌肉细胞中引发信号级联反应，导致包括乙酰胆碱受体（AChRs）在内的突触后蛋白聚集。我们研究了一氧化氮合酶（NOS）活性对于胚胎NMJ处聚集蛋白诱导的突触后AChRs聚集在体内和培养的肌肉细胞中是否是必需的。抑制NOS可使胚胎非洲爪蟾NMJ处的AChR聚集减少50%至90%，而在这些突触处过表达NOS可使AChR聚集面积增加2至3倍。NOS抑制剂完全阻断了培养的胚胎肌肉细胞中聚集蛋白诱导的AChR聚集。在没有聚集蛋白的情况下，向肌肉细胞中应用NO供体可诱导AChR聚集。我们的结果表明，NOS活性对于胚胎NMJ的突触后分化是必需的，并且NOS可能是骨骼肌细胞聚集蛋白-MuSK信号通路的参与者。
