Role of sub-membranous phase separation in the regulation of myelin membrane structure and function

膜下相分离在髓磷脂膜结构和功能调节中的作用

• 批准号: 418638383
• 负责人: Professor Dr. Mikael Jakob Simons
• 金额: --
• 依托单位: Institut für Zellbiologie des Nervensystems
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418638383?language=en
• 关键词: Role; sub; membranous; phase; separation

Myelin is a membrane of vital importance for the function of the nervous system. It is formed by the spiral wrapping of oligodendrocyte plasma membrane around axons of the central nervous system. The result is the formation of highly abundant, tightly packed membrane stacks with unique structural properties. Noteworthy features of myelin are richness in lipid, tight packing of its components and high physical stability. Previously, myelin was thought to be non-dynamic, but it is now clear that myelination contributes to brain plasticity being modifiable by experience. For example, myelin sheaths can shrink or grow in size in adult animals. Mechanistically, it is difficult to understand how a multilayered compacted membrane stack can change its structure after its formation. Here, we will test the hypothesis that phase transitions of the myelin basic proteins (MBP) at the cytosolic membrane interface of the myelin membrane regulate this process. We have previously shown that membrane compaction is mediated by a phase transition of MBP molecules into a cohesive meshwork. In its unassembled state MBP molecules are non-interactive, whereas the assembly uncovers its strongly adhesive properties that bring negatively charged membranes closely together. Phase transitions occurring in the cytosol are an emerging field in biology, but almost nothing is known about their role in the sub-membranous space. Here, we propose to study the role of cytosolic, sub-membranous phase transitions in regulating myelin membrane structure and function. We propose that such phase separations control the generation of an adhesive liquid regulating the opening and the closing of the myelin membrane stack to allow myelin remodeling. Another important aim is the study of the role of uncontrolled phase transitions in mediating the breakdown of myelin in demyelinating diseases.

髓鞘是一种对神经系统功能至关重要的膜。它是由少突胶质细胞质膜螺旋缠绕在中枢神经系统轴突周围形成的。其结果是形成具有独特结构特性的高度丰富的紧密堆积的膜堆。髓磷脂的显著特征是富含脂质、其组分的紧密包装和高物理稳定性。以前，髓鞘被认为是非动态的，但现在很清楚，髓鞘有助于大脑的可塑性是可修改的经验。例如，髓鞘在成年动物中可以缩小或增大尺寸。从机理上讲，难以理解多层压实膜堆在其形成后如何改变其结构。在这里，我们将测试的假设，髓鞘碱性蛋白（MBP）在髓鞘膜的胞质膜界面的相变调节这一过程。我们以前已经表明，膜压实介导的MBP分子的相变成一个有凝聚力的网络。在其未组装状态下，MBP分子是非相互作用的，而组装揭示了其强烈的粘合性能，使带负电荷的膜紧密结合在一起。发生在胞质溶胶中的相变是生物学中的一个新兴领域，但几乎没有人知道它们在膜下空间中的作用。 在这里，我们建议研究的作用，胞质，亚膜相变在调节髓鞘膜的结构和功能。我们提出，这种相分离控制产生的粘合剂液体调节开放和关闭的髓鞘膜堆栈，以允许髓鞘重塑。另一个重要的目的是研究不受控制的相变在介导脱髓鞘疾病中髓鞘分解中的作用。