Membrane microdomains in myelin

髓磷脂中的膜微区

• 批准号: 357103-2008
• 负责人: DeBruin, Lillian
• 金额: $ 1.82万
• 依托单位: Wilfrid Laurier University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=459831
• 关键词: Membrane; microdomains; myelin

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.

髓鞘是包裹在轴突外的多层膜，使神经冲动能够快速传递。髓鞘膜内有独特的区域或微域，它们是髓鞘发育和维持所必需的功能实体。微结构域的常见结构成分是流动性较差的脂质，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具有不同的亲和力。脂筏是一种特殊类型的微结构域，存在于大多数细胞膜中，富含脂锚定蛋白。虽然在膜上观察到小泡是瓶状的内陷，但在髓磷脂或髓磷脂产生细胞中没有发现这种特殊的微结构域。其他髓磷脂微结构域，如富含小洞蛋白的微结构域、间隙连接和径向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，有必要将每种微结构域从体膜中分离出来并表征它们的蛋白质组。通过差异提取技术，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髓鞘发育和维持中的特定功能作用。根据这些知识，我们可以研究髓磷脂微结构域在多种疾病和中枢神经系统“白质”紊乱（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。