Mechanisms of myelin membrane biogenesis in the central nervous system

中枢神经系统髓磷脂膜生物发生机制

• 批准号: 230695875
• 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: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/230695875?language=en
• 关键词: Mechanisms; myelin; membrane; biogenesis; central

Myelin is an electrical insulator essential for the rapid conduction of nerve impulses in the central nervous system. In order to do so, myelin requires a unique lipid and protein composition. Our recent findings demonstrate that oligodendrocytes generate a barrier that functions as a physical filter to form the lipid-rich myelin membrane sheets. Myelin basic protein establishes this molecular sieve and restricts the diffusion of proteins into myelin. This mechanism generates the anisotropic membrane organization of oligodendrocytes that facilitates the assembly of highly insulating membranes. The aim of this proposal is to determine the underlying principles in the formation of this barrier. We propose a diffusion-trap theory of myelin growth. In addition, we want to test whether myelin basic protein is subject to membrane-dependent cooperative assembly into two-dimensional protein arrays. The model will be tested experimentally both in vitro and in vivo with a wide spectrum of approaches including microscopy, biochemistry, reconstitution assays and mathematical modeling.

髓鞘是中枢神经系统中神经冲动快速传导所必需的电绝缘体。为了做到这一点，髓鞘需要独特的脂质和蛋白质组成。我们最近的研究结果表明，少突胶质细胞产生一个屏障，作为一个物理过滤器，以形成富含脂质的髓鞘膜片。髓鞘碱性蛋白建立了这种分子筛，并限制蛋白质扩散到髓鞘中。这种机制产生了各向异性的膜组织的少突胶质细胞，促进高度绝缘膜的组装。本提案的目的是确定形成这一障碍的基本原则。我们提出了髓鞘生长的扩散陷阱理论。此外，我们想测试髓鞘碱性蛋白是否会受到膜依赖性的合作组装成二维蛋白质阵列。该模型将在体外和体内进行实验测试，采用广泛的方法，包括显微镜，生物化学，重建测定和数学建模。

项目成果

Loss of electrostatic cell-surface repulsion mediates myelin membrane adhesion and compaction in the central nervous system

• DOI: 10.1073/pnas.1220104110
• 发表时间: 2013-02-19
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Bakhti, Mostafa;Snaidero, Nicolas;Simons, Mikael
• 通讯作者: Simons, Mikael

Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system.

• DOI: 10.1016/j.devcel.2015.05.013
• 发表时间: 2015-07-27
• 期刊: Developmental cell
• 影响因子: 11.8
• 作者: Nawaz S;Sánchez P;Schmitt S;Snaidero N;Mitkovski M;Velte C;Brückner BR;Alexopoulos I;Czopka T;Jung SY;Rhee JS;Janshoff A;Witke W;Schaap IAT;Lyons DA;Simons M
• 通讯作者: Simons M