Building the vertebrate neuromuscular synapse
Building the vertebrate neuromuscular synapse
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DOI：
10.1002/neu.10137
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发表时间：
2002-12-01
期刊：
影响因子：
--
通讯作者：
Burden, SJ
中科院分区：
文献类型：
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作者：
Burden, SJ
神经肌肉突触在运动神经元、肌肉纤维和许旺细胞之间的一系列复杂相互作用之后形成，其最终形成高度特化的突触后膜和高度分化的神经末梢（Son和Thompson，1995; Burden，1998; Sanes和Lichtman，2001; Schaeffer等人，2001年）的报告。在成年肌肉中，运动轴突终末位于肌细胞膜的浅凹陷处，其进一步内陷到深而规则的褶皱中，称为连接后褶皱。乙酰胆碱受体（AChRs）和其他蛋白质集中在这些postjunctional褶皱的波峰，而其他蛋白质，包括钠通道，富集在postjunctional褶皱的波谷。编码许多这些肌源性突触蛋白的基因优先在位于突触位点附近的肌纤维核中转录，导致编码的mRNA在突触核附近积累。神经末梢同样在空间上有组织，其亚结构组织反映了突触后膜的组织。突触囊泡聚集在突触前膜的特化区附近，称为活动区，这是突触囊泡融合的位点。活动带以规则的间隔组织，并与接合后褶皱的口部精确对齐。活性区和连接后褶皱的精确记录确保乙酰胆碱在释放后的微秒内遇到高浓度的AChR，从而促进突触传递。突触前膜和突触后膜中分子的这种精确组织掩盖了神经肌肉突触是简单突触的概念。相反，突触前和突触后膜的亚结构表明，需要空间限制突触前和突触后细胞之间的信号传导的复杂机制，需要组装突触和协调突触前和突触后分化。
Neuromuscular synapses form following a series of complex interactions between motor neurons, muscle fibers, and Schwann cells that culminate in the formation of a highly specialized postsynaptic membrane and a highly differentiated nerve terminal (Son and Thompson, 1995; Burden, 1998; Sanes and Lichtman, 2001; Schaeffer et al., 2001). In adult muscle, motor axon terminals are situated in shallow depressions of the muscle cell membrane, which is invaginated further into deep and regular folds, termed postjunctional folds. Acetylcholine receptors (AChRs) and additional proteins are concentrated at the crests of these postjunctional folds, while other proteins, including sodium channels, are enriched in the troughs of the postjunctional folds. The genes encoding many of these muscle-derived synaptic proteins are transcribed preferentially in the myofiber nuclei that are situated near the synaptic site, resulting in an accumulation of the encoded mRNAs near synaptic nuclei. The nerve terminal is likewise spatially organized, and its substructural organization reflects that of the postsynaptic membrane. Synaptic vesicles are clustered adjacent to poorly characterized specializations of the presynaptic membrane, termed active zones, which are the sites of synaptic vesicle fusion. Active zones are organized at regular intervals and are aligned precisely with the mouths of the postjunctional folds. This precise registration of active zones and postjunctional folds insures that acetylcholine encounters a high concentration of AChRs within microseconds after release, thereby facilitating synaptic transmission. This precise organization of molecules in presynaptic and postsynaptic membranes belies the concept that the neuromuscular synapse is a simple synapse. Rather, the substructure of presynaptic and postsynaptic membranes suggests that complex mechanisms, requiring spatially restricted signaling between presynaptic and postsynaptic cells, are required to assemble the synapse and to coordinate presynaptic and postsynaptic differentiation.