The structure and function of myelin oligodendrocyte glycoprotein

Myelin oligodendrocyte glycoprotein (MOG) is a quantitatively minor compone nt of CNS myelin whose function remains relatively unknown. As MOG is an au toantigen capable of producing a demyelinating multiple sclerosis-like dise ase in mice and rats, much of the research directed toward MOG has been imm unological in nature. Although the function of MOG is yet to be elucidated, there is now a relatively large amount of biochemical and molecular data r elating to MOG. Here we summarize this information and include our recent f indings pertaining to the cloning of the marsupial MOG gene. On the basis o f this knowledge we suggest three possible functions for MOG: (a) a cellula r adhesive molecule, (b) a regulator of oligodendrocyte microtubule stabili ty, and (c) a mediator of interactions between myelin and the immune system , in particular, the complement cascade. Given that antibodies to MOG and t o the myelin-specific glycolipid galactocerebroside (Gal-C) both activate t he same signaling pathway leading to MBP degradation, we propose that there is a direct interaction between the membrane-associated regions of MOG and Gal-C. Such an interaction may have important consequences regarding the m embrane topology and function of both molecules. Finally, we examine how po lymorphisms and/or mutations to the MOG gene could contribute to the pathog enesis of multiple sclerosis.