Membrane topology of the myelin/oligodendrocyte glycoprotein.
Myelin/oligodendrocyte glycoprotein (MOG), a specific component of the mammalian central nervous system, is located on the surface of the oligodendrocyte plasma membrane and the outermost lamellae of mature myelin; it is expressed during the latter steps of myelinogenesis. It has been shown that MOG may play a pathological role in autoimmune demyelinating diseases of the central nervous system, although its physiological function remains unknown. MOG is an integral membrane glycoprotein with an extracellular immunoglobulin-like domain and two hydrophobic segments which were predicted to be membrane-spanning on the basis of hydropathy analysis. As a first step in elucidation of MOG function, we have investigated its membrane topology, combining immunofluorescence studies on cultured oligodendrocytes and MOG-transfected Chinese hamster ovary cells with biochemical analyses, including in vitro translation, membrane insertion and protease-digestion assays. Our results 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 whereas the second hydrophobic region appears to be semi-embedded in the lipid bilayer, lying partially buried in the membrane with its N-terminal and C-terminal boundaries facing the cytoplasm.
della Gaspera
B
B
Laboratoire de Neurogénétique Moléculaire, URA 1488 CNRS, Université de Paris VI, Institut des Neurosciences, France.
Pham-Dinh
D
D
Roussel
G
G
Nussbaum
J L
JL
Dautigny
A
A
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002268:Carboxypeptidases / Q000378:metabolism; D043402:Cathepsin A; D006224:Cricetinae; D019286:Endopeptidase K / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000737:chemistry; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry* / Q000235:genetics; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000737:chemistry; D009836:Oligodendroglia / Q000737:chemistry; D014176:Protein Biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection / Q000235:genetics
C571326:MOG protein, human; D008562:Membrane Glycoproteins; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D002268:Carboxypeptidases; C468629:CTSA protein, human; D043402:Cathepsin A; D019286:Endopeptidase K