MYELIN ASSOCIATED GLYCOPROTEIN & MYELIN OLIGODENDROCYTE GLYCOPROTEIN

MAG is a cell surface member of the immunoglobulin- like (Ig) superfamily, with five extracellular Ig-like domains, a single transmembrane domain, and one of two alternatively spliced short cytoplasmic tails (Trapp, 1990). It is coded by a single gene that is conserved among vertebrates (Arquint et al., 1987); human and rodent MAGs are 95% identical at the amino acid level over the entire extracellular expressed domain (five Ig like domains, 500 amino acids). MAG is produced only in myelinating glial cells: oligodendrocytes in the CNS and Schwann cells in the PNS. Although it is a quantitatively minor myelin protein (1% of CNS and 0.1% of PNS myelin protein), MAG is not expressed uniformly throughout myelin. In the CNS, MAG is located on the innermost (periaxonal) non-compacted myelin wrap (Bartsch et al., 1989). In the PNS, MAG is found on periaxonal myelin and on other noncompacted myelin (paranodal loops, Schmitt-Lanterman incisures, and the mesaxon; Trapp et al., 1989).

The myelin-associated glycoprotein (MAG) is a 100 kDa transmembrane glycoprotein that is selectively localized in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths, suggesting that it functions in glia–axon interactions in both the PNS and CNS. It is important for the normal formation and maintenance of myelinated axons, although it is currently well known as one of several white matter inhibitors of axonal regeneration and as an antigen for IgM monoclonal antibodies that cause demyelinating peripheral neuropathy.

 

Fig. 1: Electron micrographs of PNS and CNS myelin-sheaths color coded to show the locations of MAG and other myelin proteins.

 Electron micrographs of PNS and CNS myelin-sheaths colour coded to show the locations of MAG and other myelin proteins. The cytoplasm of the Schwann cell and oligodendrocyte are highlighted in green. Protein zero (P0), myelin basic protein (MBP), P2 protein, and peripheral myelin protein-22 (PMP-22) are components of the layered compact myelin (gray) in the PNS, whereas proteolipid protein and MBP are the major proteins of CNS compact myelin (gray). In contrast to the proteins of compact myelin, MAG (yellow) is localized in periaxonal Schwann cell and oligodendroglial membranes of both PNS and CNS myelin sheaths, where it projects into the periaxonal space and participates in glia–axon interactions. Myelin-oligodendrocyte glycoprotein (red) is specific to the CNS and localized on the outside surfaces of myelin sheaths and oligodendrocytes, where it is accessible to components in the external environment. The PNS sheath is much larger than the CNS sheath, so magnification of the CNS sheath is about 10-fold greater. Ax, axon. This figure was adapted with permission from Fig. 2 in Quarles, (2002).

The myelin-associated glycoproteins were greatly enriched in the heavy-myelin and membrane subfractions when compared with light myelin. Furthermore, these glycoproteins have also been identified in whole myelin isolated from animals up to 90 days old (Mena, 1978).

MYELIN OLIGODENDROCYTE GLYCOPROTEIN:

         

MOG is primarily localized at the surface of the outermost myelin lamellae and the oligodendrocyte plasma membrane. The oligodendrocytes myelin glycoprotein (OMgp) is a glycosylphosphatidylinositol-anchored protein expressed by neurons and oligodendrocytes in the central nervous system (CNS) (Habib et al., 1998; Wang et al., 2002).

MOG was first identified by a polyclonal antibody directed against an antigen called M2 that induces autoimmune encephalomyelitis in the guinea pig. MOG was first identified as the antigen responsible for the demyelination observed in animals injected with whole CNS homogenate; it was later identified as a minor glycoprotein specific for CNS myelin (Lebar et al., 1986, 1976). MOG was further characterized by immunological methods, immunohistochemistry, and Western blot, using a mouse monoclonal antibody against glycoproteins of rat cerebellum (Linington et al., 1984).

MOG is a type I integral membrane protein possessing a single extracellular Ig variable domain (Ig-V) (3, 13, 14). The amino acid sequence of MOG is highly conserved among animal species (90%), indicative of an important biological function. MOG is specifically expressed in the CNS on the outermost lamellae of the myelin sheath as well as the cell body and processes of oligodendrocytes (Johns et al., 1999). The developmentally late expression of MOG correlates with the later stages of myelinogenesis, suggesting that MOG has a role in the completion, compaction, and or maintenance of myelin, further suggesting that MOG has an adhesive function within the CNS (Johns et al., 1999). Consistent with MOG’s possible adhesive role in the CNS, a homodimeric form of MOG has not only been observed after isolation from the CNS but has additionally been observed in situ (Slavin et al., 1997).

The function of MOG, expressed at the surface of the oligodendrocytes and myelin sheaths, remains unknown. Its late expression during ontogenesis, together with its external localization on the myelin sheaths, has led some authors to propose a specific role for MOG in the maintenance of myelin integrity (Birling et al., 1993), or as a signal to arrest further myelination (Gardinier et al., 1992).

Glycoproteins have been implicated in a number of membrane-mediated events (Gottleib et al., 1974). The glycoproteins of myelin demonstrated in the present study and in other studies (Zanetta et al., 1977; McIntyre et al., 1979; Quarles et al., 1979; Lane & Fagg, 1980; Poduslo et al., 1980) may have roles in the formation and maintenance of this membrane structure or in the axonal-myelin interaction.