Cellular and Molecular Basis of Agrin-Induced Synaptic Organization

长期以来，细胞外基质一直被认为是组织发育和再生的支架。最近，基质被证明对细胞分化有更具体的影响。在再生肌肉的情况下，研究表明，与基质的突触部分相关的分子指导着肌纤维和神经末梢上特定成分的积累。虽然已经确定了神经和肌肉的功能成分，但关于它们是如何结合在一起形成突触传递所需的有序排列，人们知之甚少。尼特金博士将研究细胞外基质因子在神经肌肉接头突触结构发展中的作用。在再生过程中，与基质相关的因素指导突触前和突触后成分的分化。尼特金博士和他的同事们将专注于集聚蛋白，这是一种基质分子，可以在培养中生长的肌管上诱导出离散的突触样斑块。他们将在培养中使用细胞和分子方法来研究突触形成的以下方面：(1)活性分子的生化性质是什么？(2)集聚蛋白是如何整合到神经肌肉连接处的细胞外基质中的？(3)集聚蛋白是如何与肌管相互作用导致突触分化的？这些实验的结果将增加我们对突触组织机制的理解，并最终有助于设计促进神经组织再生的临床策略。

The extracellular matrix has long been recognized as a scaffold for developing and regenerating tissues. Recently the matrix has been shown to have more specific effects on cellular differentiation. In the case of regenerating muscle, studies demonstrate that molecules associated with the synaptic portion of the matrix direct the accumulation of specific components on myofibers and nerve terminals. Although the functional components of nerve and muscle have been identified, little is known about how they are brought together into the orderly arrangement necessary for synaptic transmission. Dr. Nitkin will examine the role of extracellular matrix factors in the development of synaptic structure at the neuromuscular junction. During regeneration, factors associated with the matrix direct the differentiation of both pre- and postsynaptic elements. Dr. Nitkin and his colleagues will focus on agrin, a matrix molecule that induces discrete synapse-like patches on myotubes grown in culture. They will use cellular and molecular approaches in culture to examine the following aspects of synapse formation: (1) What is the biochemical nature of the active molecule? (2) How is agrin integrated into the extracellular matrix at the neuromuscular junction? (3) How does agrin interact with myotubes to bring about synaptic differentiation? The results of these experiments will increase our understanding of the mechanisms of synapric organization, and may eventually contribute to the design of clinical strategies for facilitating regeneration of nervous tissue.