Membrane topology of the myelin/oligodendrocyte glycoprotein

Myelin/oligodendrocyte glycoprotein (MOG), a specific component of the mamm alian central nervous system, is located on the surface of the oligodendroc yte plasma membrane and the outermost lamellae of mature myelin; it is expr essed during the latter steps of myelinogenesis, It has been shown that MOG may play a pathological role in autoimmune demyelinating diseases of the c entral nervous system, although its physiological function remains unknown. MOG is an integral membrane glycoprotein with an extracellular immunoglobu lin-like domain and two hydrophobic segments which were predicted to be mem brane-spanning on the basis of hydropathy analysis. As a first step in eluc idation of MOG function, we have investigated its membrane topology, combin ing immunofluorescence studies on cultured oligodendrocytes and MOG-transfe cted Chinese hamster ovary cells with biochemical analyses, including in vi tro translation, membrane insertion and protease-digestion assays. Our resu lts indicate that the C-terminal tail of MOG is located into the cytoplasm, and that only the first hydrophobic region of MOG spans the membrane where as the second hydrophobic region appears to be semi-embedded in the lipid b ilayer, lying partially buried in the membrane with its N-terminal and C-te rminal boundaries facing the cytoplasm.