Membrane microdomains in myelin

髓磷脂是一种多层膜，包裹着轴突，使神经冲动能够快速传递。在髓磷脂膜内，存在独特的区域或微结构域，其是适当的髓磷脂发育和维持所必需的功能实体。微区的共同结构组分是较少流动的脂质，例如鞘糖脂和胆固醇。不同类型的微结构域对某些类型的蛋白质的亲和力不同。 脂筏是一种特殊类型的微区，存在于大多数细胞膜中，富含脂质锚定蛋白。虽然小窝已被观察到作为瓶形内陷在膜，这种特殊的微域尚未发现在髓鞘或髓鞘生产细胞。其他髓鞘微区如小窝蛋白富集微区、间隙连接和放射状成分可能参与复杂的信号网络。为了确定髓鞘中各种微结构域的作用，有必要将每种类型从散装膜中分离出来并表征其蛋白质组。利用差异提取技术，我们将分离每个微结构域，并通过二维凝胶电泳和多维蛋白质鉴定分析，我们将确定蛋白质组成。对多蛋白复合物的进一步分析将提示其在髓鞘发育和维持中的特定功能作用。从这些知识中，我们可以研究髓鞘微结构域在CNS“白色物质”的各种疾病和病症如多发性硬化症或肾上腺脑白质营养不良中的重塑，并确定可用于治疗策略的分子靶点。

The myelin is a multi-layered membrane that ensheathes the axon, enabling rapid transmission of the nerve impulse. Within the myelin membrane there are unique regions or microdomains that are functional entities necessary for proper myelin development and maintenance. The common structural components of microdomains are less-fluid lipids, such as glycosphingolipids and cholesterol. The different types of microdomains vary in their affinity for certain classes of proteins. A specific type of microdomains, lipid rafts are found in most cellular membranes and are enriched in lipid-anchored proteins. Although caveolae have been observed as flask-shaped invaginations in the membrane, this particular microdomain has not been found in myelin or the myelin-producing cells. Other the myelin microdomains such as caveolin-enriched microdomains, gap junctions, and the radial component may be involving in complex signaling networks. To determine the roles of the various microdomains in myelin, it is necessary to separate each type from the bulk membrane and characterize their proteome. With differential extractions techniques we will isolate each microdomain, and with 2D gel electrophoresis and multi-dimensional protein identification analysis we will determine the protein composition. The further analysis of multi-protein complexes will suggest specific functional roles in the development and maintenance of the myelin sheath. From this knowledge we can investigate the remodeling of myelin microdomains in various diseases and disorders of CNS "white matter" such as multiple sclerosis or adrenoleukodystropy, and determine molecular targets which can be used in therapeutic strategies.