Mechanisms of myelin membrane biogenesis in the central nervous system

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。

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.