Molecular Genetics of Demyelination: New Wrinkles on an Old Membrane

into question the common assumption that the layers of the myelin sheath have a high electrical resistance. What Are the Functions of the The Structure and Function of Myelin Myelin is one of the fundamental adaptations of verte-Myelin Components? While the individual components may normally function brates. By limiting axonal depolarization to nodes of Ranvier, the periodic interruptions in myelin, it increases as part of the macromolecular structure of compact myelin, they have been examined in isolation. The func-axonal conduction velocity. Its multilamellar structure results from the spiral wrapping of specialized cell mem-tion of protein zero (P 0), the main intrinsic membrane protein of mammalian PNS myelin, is the best under-brane around an axon (Figure 1A). The apposed external surfaces of the membrane form the intraperiod lines, stood. It has a single extracellular IgG-like domain and a basic cytoplasmic domain that have been proposed and the cytoplasmic proteins form the major dense line. These alternating intraperiod and major dense lines give to hold together, respectively, the extra-and intracellular surfaces of compact myelin. X-ray crystallography re-myelin its characteristic appearance in electron micro-graphs (Figure 1B). vealed that P 0 has an overall structure that is similar to other members of the immunoglobulin superfamily, and Two distinct cell types form myelin, oligodendrocytes in the CNS and Schwann cells in the PNS, and the com-that the extracellular domain of P0 forms tetramers, with four molecules arranged around a central hole (Shapiro pact myelin that each produces is structurally similar but chemically distinct (Figure 2). CNS and PNS myelin et al., 1996). Assuming that P0 also forms tetramers in the plane of the cell membrane, these tetramers may consist mostly of lipids, including cholesterol, glycolip-ids, and specific and overlapping sets of proteins. These interact with their counterparts on the apposing cell membrane, forming a lattice that holds the apposed components are so highly enriched that myelin has been likened to a liquid crystal, in which individual compo-extracellular surfaces together. The basic cytoplasmic domain may bind to intracellular anionic lipids, thereby nents form macromolecular complexes with themselves and each other. Such an orderly structure could require holding the intracellular surfaces together. Since P 0 is an immunoglobulin superfamily member and is found in a precise stoichiometric relationship of the individual components, so that either increasing or decreasing the CNS and PNS myelin of fishes, it appears that this cell adhesion molecule was co-opted 500 million years …