Agrin-induced clustering of acetylcholine receptors: a cytoskeletal link.
Agrin-induced clustering of acetylcholine receptors: a cytoskeletal link.
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集聚蛋白诱导的乙酰胆碱受体聚集：细胞骨架链接。
DOI：
10.1083/jcb.126.1.1
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发表时间：
1994-07
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突触连接的形成涉及突触前和突触后细胞的局部分化，这是发育过程中信息分子双向交换的结果。在一个被充分研究的突触，神经肌肉连接（NMJ）'中，agrin被认为在运动神经元诱导的肌肉突触分化中起重要作用。Agrin是运动神经元在突触形成时合成的细胞外基质蛋白，可诱导培养肌细胞表面突触分子聚集（详见McMahan， 1990）。分子分析表明，agrin是一个'~ 220 kD的蛋白家族，由选择性剪接产生，包含许多其他细胞外蛋白已知的结构基序（图1；Rupp et al., 1991; Tsim et al., 1992）。全长重组agrin，以及截断的可溶性形式，诱导烟碱乙酰胆碱受体（AChR）聚集（Campanelli等，1991；Ruegg等，1992；Ferns等，1992,1993）。AChR簇也能在培养的肌管上自发形成，这表明这种簇的机制是由肌肉贡献的。虽然运动神经元和肌肉都能合成agrin，但抗体抑制实验表明，培养中突触的形成需要运动神经元衍生的agrin，而不是肌肉衍生的agrin （Reist et al., 1992）。在这里，我们回顾了agrin在突触发生中的作用，重点关注了agrin活性的结构要求以及最近描述的agrin- dystro聚糖相互作用对agrin诱导AChR聚集机制模型的影响。
ORMATION of synaptic connections involves the localized differentiation of pre-and postsynaptic cells as the result of a bidirectional exchange of information molecules during development. At a well-studied synapse, the neuromuscular junction (NMJ)', agrin is thought to play an important role in the synaptic differentiation of the muscle induced by the motorneuron. Agrin is an extracellular matrix protein synthesized by motorneurons at the time of synapse formation, which can induce the clustering of synaptic molecules on the surface of culture muscle cells (for review see McMahan, 1990). Molecular analysis has shown that agrin is a family of proteins of'~ 220 kD that are produced by alternative splicing and that contain a number of structural motifs known from other extracellular proteins (Fig. 1; Rupp et al., 1991; Tsim et al., 1992). Full-length recombinant agrin, as well as truncated soluble forms, induce the clustering of nicotinic acetylcholine receptors (AChR)(Campanelli et al., 1991; Ruegg et al., 1992; Ferns et al., 1992, 1993). AChR clusters also form spontaneously on cultured myotubes, suggesting that the machinery for clustering is contributed by muscle. Although both motorneurons and muscles synthesize agrin, antibody inhibition experiments showed that motorneuron-derived agrin, but not the muscle-derived form, is required for synapse formation in culture (Reist et al., 1992). Here, we review the role of agrin in synaptogenesis, focusing on the structural requirements for agrin activity and implications of the recently described agrin-dystroglycan interaction for models of the mechanism of agrin-induced AChR clustering.