The structure and function of myelin oligodendrocyte glycoprotein

Myelin oligodendrocyte glycoprotein (MOG) is a quantitatively minor component of CNS myelin whose function remains relatively unknown. As MOG is an autoantigen capable of producing a demyelinating multiple sclerosis-like disease in mice and rats, much of the research directed toward MOG has been immunological in nature. Although the function of MOG is yet to be elucidated, there is now a relatively large amount of biochemical and molecular data relating to MOG. Here we summarize this information and include our recent findings pertaining to the cloning of the marsupial MOG gene. On the basis of this knowledge we suggest three possible functions for MOG: (a) a cellular adhesive molecule, (b) a regulator of oligodendrocyte microtubule stability, and (c) a mediator of interactions between myelin and the immune system, in particular, the complement cascade. Given that antibodies to MOG and to the myelin-specific glycolipid galactocerebroside (Gal-C) both activate the 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 membrane topology and function of both molecules. Finally, we examine how polymorphisms and/or mutations to the MOG gene could contribute to the pathogenesis of multiple sclerosis.