Myelin sheaths are formed around axons by extending, biochemically modifying and spiraling plasma membranes of Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Because glycoproteins are prominent components of plasma membranes, it is not surprising that they have important roles in the formation, maintenance and degeneration of myelin sheaths. The emphasis in this review is on four integral membrane glycoproteins. Two of them, protein zero (P0) and peripheral myelin protein-22 (PMP-22), are components of compact PNS myelin. The other two are preferentially localized in membranes of sheaths that are distinct from compact myelin. One is the myelin-associated glycoprotein, which is localized at the inside of sheaths where it functions in glia-axon interactions in both the PNS and CNS. The other is the myelin-oligodendrocyte glycoprotein, which is preferentially localized on the outside of CNS myelin sheaths and appears to be an important target antigen in autoimmune demyelinating diseases such as multiple sclerosis.

Myelination was studied in aggregating cell cultures derived from mechanically 15- to 16-day fetal rat brains. Myelin basic protein (MBP) and myelin-associated glycoprotein (MAG) were localized immunocytochemically in 20-micrometers-thick Vibratome and 1-micrometer-thick Epon sections at 15, 20, 25, and 30 days in vitro. The occurrence of these proteins was correlated with the ultrastructural appearance of oligodendrocytes and myelin sheaths and with biochemical levels of MBP, MAG, and the myelin-related enzyme, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). MBP appeared in ultrastructurally immature oligodendrocyte cytoplasm at 15 days in vitro. As oligodendrocytes developed a more differentiated fine structure, MBP and MAG antisera stained oligodendrocyte processes and myelin sheaths. Immunostaining in Vibratome sections demonstrated that MBP was detectable in oligodendrocytes and myelin prior to MAG. At 25 days in vitro, all Vibratome sections contained MBP- and MAG-stained oligodendrocytes and myelin sheaths. Radioimmunoassays for MBP and MAG and enzyme assays for CNP in whole homogenates of the aggregates revealed that each of these components increased with the progression of myelination. However, MBP only reached 8% of the level in adult rat brain, while MAG and CNP increased to more than half of the adult level. The protein composition of myelin purified from 30-day aggregates resembled that of myelin purified from immature rat brain.