Cellular and Molecular Basis of Agrin-Induced Synaptic Organization

细胞外基质长期以来被认为是支架 用于组织的发育和再生 最近，Matrix 已经被证明对细胞有更具体的影响 分化 在再生肌肉的情况下，研究 证明了与突触部分相关的分子 矩阵的直接积累的具体组成部分， 肌纤维和神经末梢。 虽然功能 神经和肌肉的成分已经被确定， 知道他们是如何被带到有序的 突触传递所必需的排列。 尼特金博士将研究细胞外基质因子的作用 在神经肌肉突触结构的发育中， 交界处。 在再生过程中， 基质指导突触前和突触后的分化 元素 尼特金博士和他的同事们将重点研究agrin， 一种基质分子，可诱导细胞表面形成离散的突触样斑块， 培养中生长的肌管。 他们将使用细胞和分子 在文化中的方法来检查突触的以下方面 （1）活性物质的生物化学性质是什么？ 分子？ (2)聚集蛋白是如何整合到细胞外 神经肌肉接头处的基质 (3)agrin怎么样 与肌管相互作用，从而导致突触分化？ 这些实验的结果将增加我们对 突触组织的机制，并可能最终 有助于设计临床策略， 神经组织的再生

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.