Cellular and Molecular Basis of Agrin-Induced Synaptic Organization

集聚蛋白诱导的突触组织的细胞和分子基础

• 批准号: 8707530
• 负责人: Edward Bonder
• 金额: $ 25.28万
• 依托单位: Rutgers University New Brunswick
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-15 至 1992-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8707530&HistoricalAwards=false
• 关键词: Cellular; Molecular; Basis; Agrin; Induced

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.

长期以来，细胞外基质被认为是发展和再生组织的支架。 最近，矩阵已显示对细胞分化具有更具体的影响。 在肌肉再生的情况下，研究表明，与基质的突触部分相关的分子将特定成分在肌纤维和神经末端的积累。 尽管已经确定了神经和肌肉的功能成分，但对于如何将它们聚集到突触传播所必需的有序排列中，知之甚少。 Nitkin博士将检查细胞外基质因子在神经肌肉结的突触结构发展中的作用。 在再生过程中，与矩阵有关的因素指导突触前和突触后元素的分化。 Nitkin博士及其同事将专注于Agrin，这是一种基质分子，可在文化中诱导离散的突触样斑块。 他们将在培养中使用细胞和分子方法来检查突触形成的以下方面：（1）活性分子的生化性质是什么？ （2）如何将Agrin整合到神经肌肉连接处的细胞外基质中？ （3）Agrin如何与肌管相互作用以实现突触分化？ 这些实验的结果将增加我们对同时组织机制的理解，并最终可能有助于设计促进神经组织再生的临床策略。