US-France Cooperative Research: Localization & Regulation of Cell Adhesion Molecules & Substrate Adhesion Molecules During Development & Regeneration of the Neuromuscular Sys

美法合作研究：本地化

• 批准号: 8815537
• 负责人: Gerald Edelman
• 金额: $ 1.23万
• 依托单位: Rockefeller University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-06-15 至 1992-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8815537&HistoricalAwards=false
• 关键词: US; France; Cooperative; Research; Localization

This award will support collaborative studies between Dr. Gerald Edelman and his research group at the Neurosciences Institute, Rockefeller University and Dr. Francois Rieger, Unite de Recherche de Biologie et Pathologie Neuromusculaires, Centre National de la Recherche Scientifique, Paris, France. Dr. Edelman, a Nobel Prize winner and eminent researcher in the proposed topic, has collaborated successfully with Dr. Rieger in the past. The neuromuscular system is a complex supracellular structure composed of a number of different cell types: sensory and motor neurons, Schwann cells, muscle cells, fibroblasts, and various support cells. The development, maintenance, and physiological functions of the neuromuscular system depend upon specialized structures, including the neuromuscular junction, the myotendinous junction, and the nodes of Ranvier. In previous research Drs. Edelman and Rieger showed that three glycoproteins involved in cell-cell adhesion are localized to these privileged sites and vary in amount and distribution during development and regeneration of neuromuscular contacts: the neural cell adhesion molecule, N-CAM, the neuron-glia cell adhesion molecule, Ng-CAM, and cytotactin, an extracellular matrix protein. The localization of these molecules was altered in mutant animals with various cellular defects and antibodies to N-CAM blocked the appropriate reinnervation patterns after injury, inhibiting reformation of synapses at old synaptic sites and allowing for extrasynaptic nerve-muscle contacts. The patterns of expression of these molecules correlate with those of other neuromuscular proteins, including acetylcholinesterase, and voltage-dependent calcium channels. During the next phase of collaboration, the investigators will examine the detailed basis for the localized pattern of expression of adhesion molecules and neuromuscular proteins, focusing particularly on cytoskeletal interactions. They will also use cDNA clones specific for muscle forms of N-CAM to transfect cells and produce transgenic animals. These joint experiments would be difficult to accomplish in either laboratory alone. The expertise of Dr. Rieger and his colleagues in electron microscopy, neurophysiology and mutant strains of mice will complement the expertise of Dr. Edelman and his group in the isolation and characterization of cell adhesion molecules, molecular biological techniques, fluorescence microscopy and the production and screening of monoclonal and polyclonal antibodies. These studies should provide new insights into the formation and maintenance of structures crucial to muscle function, as well as to their aberrations in muscle disease and dysfunction.

该奖项将支持Gerald Edelman博士及其在洛克菲勒大学神经科学研究所的研究小组与Francois Rieger博士（法国巴黎国家科学研究中心生物和病理神经肌肉研究所）之间的合作研究。埃德尔曼博士是诺贝尔奖获得者，也是该主题的杰出研究员，过去曾与里格博士成功合作。神经肌肉系统是一个复杂的细胞上结构，由许多不同类型的细胞组成：感觉和运动神经元、雪旺细胞、肌肉细胞、成纤维细胞和各种支持细胞。神经肌肉系统的发育、维持和生理功能依赖于特定的结构，包括神经肌肉连接处、肌腱连接处和Ranvier淋巴结。在之前的研究中。Edelman和Rieger表明，在神经肌肉接触的发育和再生过程中，有三种参与细胞-细胞粘附的糖蛋白定位于这些特权部位，其数量和分布各不相同：神经细胞粘附分子N-CAM、神经元-胶质细胞粘附分子Ng-CAM和细胞趋动素（一种细胞外基质蛋白）。在具有各种细胞缺陷的突变动物中，这些分子的定位发生了改变，N-CAM抗体在损伤后阻断了适当的神经再生模式，抑制了旧突触位点的突触改造，并允许突触外神经-肌肉接触。这些分子的表达模式与其他神经肌肉蛋白的表达模式相关，包括乙酰胆碱酯酶和电压依赖性钙通道。在下一阶段的合作中，研究人员将研究粘附分子和神经肌肉蛋白的局部表达模式的详细基础，特别关注细胞骨架相互作用。他们还将使用针对肌肉形式的N-CAM的cDNA克隆来转染细胞并生产转基因动物。这些联合实验很难单独在任何一个实验室完成。Rieger博士及其同事在电子显微镜、神经生理学和小鼠突变株方面的专业知识将补充Edelman博士及其团队在细胞粘附分子的分离和表征、分子生物学技术、荧光显微镜以及单克隆和多克隆抗体的生产和筛选方面的专业知识。这些研究应该为肌肉功能的关键结构的形成和维持，以及它们在肌肉疾病和功能障碍中的畸变提供新的见解。