Structure and Function of the Myelin‐Associated Glycoproteinsa (original) (raw)

1990, Annals of the New York Academy of Sciences

Axons exhibit complex, reciprocal interactions with myelinating glial cells, that is, Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Contact with the axon regulates the proliferation of these glial cells and determines their state of differentiation, most dramatically their elaboration and maintenance of the myelin sheath. The glial cell, in turn, influences both the topographic segregation of axonal membrane constituents and the diameter of the adjacent axonal segment. These axonal-glial interactions are essential for the formation of a mature, fully differentiated myelinated nerve fiber, an essential component of the vertebrate nervous system.' This intimate functional interrelationship is, in turn, reflected in the close apposition of the respective plasma membranes of the axon and the myelinating glial cell. These membranes are separated by a regular extracellular space of 120-140 angstroms that is actively maintained even in pathologic conditions.2 The panoply of cell surface proteins present on the apposed membranes is likely to mediate these cellular interactions as well as maintain the periaxonal space. In addition, as they are extracellularly disposed, these proteins are potential targets in viral and immune-mediated damage to myelinated fibers. Identification and characterization of these membrane constituents should therefore provide important insights into the molecular mechanisms of these cell-cell interactions and into the pathogenesis of demyelinating diseases such as multiple sclerosis. Of the currently identified cell surface constituents of myelinating glial cells, the myelin-associated glycoproteins (MAG proteins) are the most likely candidates for mediating this interaction. These proteins are integral membrane proteins that are minor constiuents of the myelin sheath, comprising about 1% of the total protein content of CNS myelin and less than one tenth of that in PNS ~n y e l i n .~ Unlike structural components of compact myelin, such as the basic proteins or the proteolipid protein, the MAG proteins are present in noncompacted myelin membranes on the basis of fractionation studies as well as immuno-0 These studies were aided by basic research grant No.