ORGANIZATION OF THE AXON MEMBRANE

轴突膜的组织

• 批准号: 3414533
• 负责人: KIMON J ANGELIDES
• 金额: $ 18.63万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3414533
• 关键词: Schwann cells; afferent nerve; ankyrins; axon; cell adhesion; cytoskeleton; developmental neurobiology; electron microscopy; embryo /fetus tissue /cell culture; extracellular matrix; glia; glycoproteins; immunocytochemistry; immunoelectron microscopy; immunofluorescence technique; lipids; membrane proteins; membrane structure; myelination; myelinopathy; node of Ranvier; peripheral nervous system; sodium channel; spectrin

Reorganization of the axonal membrane is often associated with pathological conditions that accompany demyelinating disorders such as multiple sclerosis. This research program focuses on the molecular organization and dynamics of the axonal membrane in developing, myelinating, and demyelinated nerve in tissue culture models. We will examine the distribution of excitable membrane components by immune-fluorescence and electron microscopy in myelinated fibers in the peripheral nervous systems and those fibers that have been experimentally demyelinated. Because we are particularly interested in the dynamic changes occurring in the organization of the axon membrane during myelination, we will monitor the sequential changes in excitable membrane protein topography by digital fluorescence microscopy on single neurons in long-term cultures of sensory neurons and Schwann cells as the axons become ensheathed. The role and magnitude of intracellular and/or extracellular elements that organize the axon membrane during development, ensheathment, and demyelination will be examined by measuring the lateral mobility of sodium channels, glycoproteins, and lipids by fluorescence photobleach recovery. Cultures of sensory neurons either in the absence or presence of Schwann cells will be used to assess the contribution of axon-glial contact in modulating the organization of the axon membrane during development. The role of the ensheathing cell in maintaining nodal and internodal specializations will be examined with developing, demyelinated, and remyelinating fibers. The temporal and spatial events in the expression, assembly, and segregation of NaChs with the extracellular matrix and cytoskeleton will be examined. Specifically, we will continue to study the role of both adhesion molecules, ankyrin, and spectrin in establishing restricted membrane domains that could serve to maintain excitable membrane components to specific regions of the axon.

轴突膜的重组通常与病理性 伴随脱髓鞘疾病的病症，例如多发性 硬化症该研究计划的重点是分子组织和 轴突膜在发育、髓鞘形成和 组织培养模型中的脱髓鞘神经。 我们将通过以下方法研究可兴奋膜成分的分布： 免疫荧光和电子显微镜在有髓纤维在 周围神经系统和那些在实验中 脱髓鞘因为我们特别感兴趣的是 发生在髓鞘形成过程中轴突膜的组织中，我们 将监测可兴奋膜蛋白的连续变化 通过数字荧光显微镜对单个神经元的拓扑图， 感觉神经元和许旺细胞的长期培养， 套在鞘里细胞内和/或细胞外的作用和大小 在发育，鞘化， 和脱髓鞘将通过测量 钠通道、糖蛋白和脂质的荧光光漂白 复苏感觉神经元的培养无论是在缺乏或存在的 雪旺细胞将用于评估轴突-神经胶质细胞接触的贡献 在发育过程中调节轴突膜的组织。的 成鞘细胞在维持结和结间 专业化将检查与发展，脱髓鞘， 髓鞘再生纤维 表达式、装配和 NaChs与细胞外基质和细胞骨架的分离将是 考察具体来说，我们将继续研究两者的粘附作用 分子、锚蛋白和血影蛋白在建立限制性膜中的作用 这些结构域可以用来维持可兴奋的膜成分， 轴突的特定区域。