Role of extracellular matrix proteins and their receptors in the development of the vertebrate neuromuscular junction.
Role of extracellular matrix proteins and their receptors in the development of the vertebrate neuromuscular junction.
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DOI：
10.1002/dneu.20953
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发表时间：
2011-11
影响因子：
3
通讯作者：
Martin, Paul T.
中科院分区：
文献类型：
--
作者：
Singhal, Neha;Martin, Paul T.
脊椎动物神经肌肉接头仍然是了解突触发生机制的最佳研究模型，这是由于其相对较大的尺寸，其模式的简单性和无与伦比的实验可及性。在神经肌肉发育过程中，每个骨骼肌纤维分泌并在其细胞外表面周围沉积细胞外基质（ECM）蛋白的集合体，最终形成基底层。在神经肌肉接头处也是如此，其中运动神经贡献了额外的因素。在大多数目前的分子组成是已知的，很明显，突触ECM的成人骨骼肌是独特的组成，并含有足够的因子，以诱导突触前和突触后膜的分化。生物化学、遗传学和显微镜研究已经证实，聚集蛋白、层粘连蛋白（221、421和521）、胶原IV（α3-α6）、胶原XIII、串珠素和乙酰胆碱酯酶的ColQ结合形式都是突触ECM蛋白，在神经肌肉发育中具有重要作用。由于与这些大蛋白的膜相互作用的复杂性，它们的许多潜在受体和/或结合蛋白的作用在遗传水平上更难以评估，但是已经鉴定了MuSK-LRP 4在聚集蛋白信号传导中的作用以及整合素、肌营养不良蛋白聚糖和电压门控钙通道在层粘连蛋白依赖性表型中的作用。突触细胞外基质蛋白及其受体参与了突触发育的几乎所有方面，包括突触起始、形态、超微结构、成熟、稳定和传递。
The vertebrate neuromuscular junction remains the best-studied model for understanding the mechanisms involved in synaptogenesis, due to its relatively large size, its simplicity of patterning and its unparalleled experimental accessibility. During neuromuscular development, each skeletal myofiber secretes and deposits around its extracellular surface an assemblage of extracellular matrix (ECM) proteins that ultimately form a basal lamina. This is also the case at the neuromuscular junction, where the motor nerve contributes additional factors. Before most of the current molecular components were known, it was clear that the synaptic ECM of adult skeletal muscles was unique in composition and contained factors sufficient to induce the differentiation of both pre- and postsynaptic membranes. Biochemical, genetic and microscopy studies have confirmed that agrin, laminin (221, 421, and 521), collagen IV (α3-α6), collagen XIII, perlecan and the ColQ-bound form of acetylcholinesterase are all synaptic ECM proteins with important roles in neuromuscular development. The roles of their many potential receptors and/or binding proteins has been more difficult to assess at the genetic level due to the complexity of membrane interactions with these large proteins, but roles for MuSK-LRP4 in agrin signaling and for integrins, dystroglycan, and voltage-gated calcium channels in laminin-dependent phenotypes have been identified. Synaptic extracellular matrix proteins and their receptors are involved in almost all aspects of synaptic development, including synaptic initiation, topography, ultrastructure, maturation, stability and transmission.
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