INVESTIGATION OF MYELIN OLIGODENDROCYTE GLYCOPROTEIN MEMBRANE TOPOLOGY/

Myelin/oligodendrocyte glycoprotein (MOG) is a CNS-specific integral m embrane protein that is an atypical member of the immunoglobulin (Ig) superfamily with two potential transmembrane domains based upon hydrop athy analysis. With only one other exception, all Ig family members po ssess a single or no membrane spanning region. in order to analyze MOG membrane topology, we prepared stably transfected cells that express mouse MOG and used three domain-specific antisera to ascertain the loc alization of these hydrophilic domains. As expected, MOG's glycosylate d N-terminal Ig-like domain was identified as extracellular, because m embrane permeabilization was not required for immunoreactivity with th e MOG(1-125) antiserum. In contrast, both MOG(154-169) and MOG(198-218 ) antisera stained cells only upon permeabilization. These data indica te that only MOG's N-terminal hydrophobic domain spans the lipid bilay er, and we propose that MOG's C-terminal hydrophobic domain associates with the cytoplasmic face of the plasma membrane. As for MOG's second hydrophobic domain, it is clear that either orientation (transmembran e versus membrane-associated) would be unique among Ig-like proteins, and the implications of our proposed topology for MOG in oligodendrogl ial plasma membrane are discussed.