ORGANIZATION OF THE AXON MEMBRANE

轴突膜的重组通常与病理相关 伴随脱髓鞘疾病的病症，例如多发性脱髓鞘疾病 硬化。该研究计划的重点是分子组织和 轴突膜在发育、髓鞘形成和发育过程中的动力学 组织培养模型中的脱髓鞘神经。 我们将通过以下方式检查可兴奋膜成分的分布 有髓纤维的免疫荧光和电子显微镜 周围神经系统和那些经过实验验证的纤维 脱髓鞘。因为我们对动态变化特别感兴趣 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进行形貌分析 随着轴突的形成，感觉神经元和雪旺细胞的长期培养 被包裹。细胞内和/或细胞外的作用和重要性 在发育过程中组织轴突膜的元素，鞘， 脱髓鞘情况将通过测量侧向活动性来检查 通过荧光漂白去除钠通道、糖蛋白和脂质 恢复。在不存在或存在的情况下感觉神经元的培养 雪旺细胞将用于评估轴突-神经胶质接触的贡献 在发育过程中调节轴突膜的组织。的 鞘细胞在维持结节和结间的作用 将检查发育中、脱髓鞘和 髓鞘再生纤维。 表达、组装和表达中的时间和空间事件 NaChs 与细胞外基质和细胞骨架的分离将是 检查了。具体来说，我们将继续研究两者粘附的作用 分子、锚蛋白和血影蛋白在建立限制性膜中的作用 可以用来维持可兴奋膜成分的结构域 轴突的特定区域。

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.