Godfrey Earl W, Schwarte Russell C
Department of Pathology and Anatomy, Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA 23501, USA.
J Neurocytol. 2003 Jun-Sep;32(5-8):591-602. doi: 10.1023/B:NEUR.0000020612.87729.98.
The formation of the vertebrate neuromuscular junction (NMJ) depends on the action of neural agrin on the muscle cell. The requirement for agrin and its receptor, muscle-specific kinase (MuSK), has been well established over the past 20 years. However, the signaling mechanisms through which agrin and MuSK cause synaptic differentiation are not well understood. New evidence from studies of muscle cells in culture and in embryos indicates that nitric oxide (NO) is an effector of agrin-induced postsynaptic differentiation at the NMJ. Cyclic GMP (cGMP) production by guanylate cyclase appears to be an important downstream step in this pathway. Nitric oxide and cGMP regulate the activity of several kinases, some of which may influence interaction of dystrophin and utrophin with the actin cytoskeleton to mediate or modulate postsynaptic differentiation in muscle cells. These signaling molecules could also play a role in retrograde signaling to influence differentiation of presynaptic nerve terminals.
脊椎动物神经肌肉接头（NMJ）的形成依赖于神经聚集蛋白对肌肉细胞的作用。在过去20年里，对聚集蛋白及其受体——肌肉特异性激酶（MuSK）的需求已得到充分证实。然而，聚集蛋白和MuSK引起突触分化的信号传导机制尚不清楚。来自培养的肌肉细胞和胚胎研究的新证据表明，一氧化氮（NO）是聚集蛋白诱导NMJ突触后分化的效应器。鸟苷酸环化酶产生环磷酸鸟苷（cGMP）似乎是该途径中的一个重要下游步骤。一氧化氮和cGMP调节几种激酶的活性，其中一些激酶可能影响肌营养不良蛋白和抗肌萎缩蛋白与肌动蛋白细胞骨架的相互作用，从而介导或调节肌肉细胞中的突触后分化。这些信号分子也可能在逆行信号传导中发挥作用，以影响突触前神经末梢的分化。
