Mechanisms of myelin membrane biogenesis in the central nervous system

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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.