Polarity development in oligodendrocytes: sorting and trafficking of myelin components

In vertebrates, myelination is required for the saltatory signal conductance along the axon. At the onset of myelination, the myelinating cells, i.e., oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system, are heavily engaged in the biogenesis of membranes that are wrapped around the axon to form the myelin sheath. Although the membrane of the myelin sheath is continuous with the plasma membrane surrounding the cell body, the composition of both membrane domains is clearly distinct implying that myelinating cells are polarized cells. The coordinated manner of myelin sheath formation requires the existence of sorting and trafficking pathways to establish and maintain this highly polarized phenotype. Although in vitro data show that the formation of myelin-like membranes is an intrinsic property of oligodendrocytes, exogenous factors modulate myelination and are required for the subcompartmentation and compaction of the myelin sheath in vivo. In this paper, we discuss the sorting and trafficking of myelin proteins and lipids in oligodendrocytes in relation to polarity development and maintenance, including the role of exogenous factors, and give examples how the perturbation of trafficking pathways may contribute to the development of demyelinating diseases of the central nervous system.