Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex.

Pham-Dinh, Danielle; Mattéi, Marie Geneviève; Nussbaum, Jean Louis; Roussel, G.; Pontarotti, Pierre; Roëckel, Nathalie; Mather, Ian H.; Artzt, Karen; Lindahl, Kirsten Fischer; Dautigny, André

doi:10.1073/pnas.90.17.7990

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“…2A, lane 2), whereas treatment with N-glycosidase F reduced the size of this protein to 27 kDa (Fig. 2 A, lane 3), consistent with the molecular mass of the amino acid sequence deduced from the cDNA [19], the glycosylation of MOG at asparagine 31 [6,16] and the removal of the signal peptide, as it would be expected to occur in functional microsomal membranes. The relative molecular mass of the translated MOG is somewhat larger than that of MOG from isolated myelin.…”

Section: Resultssupporting

confidence: 56%

“…2 B, lanes 6 and 8). As expected [6,16], the Ig-like domain of MOG was detected with the anti-EC antibody only when the microsomes were first broken with Nonidet P-40 (Fig. 2 B, compare lane 5 with lane 7), indicating that the microsomes in the present experimental conditions were intact.…”

Section: Resultsmentioning

confidence: 73%

“…MOG is an integral glycoprotein [2,6,9,16,25]; comparison of the deduced cDNA sequence with that of the mature protein indicated that MOG contains a signal peptide followed by a sequence homologous to an Ig-like domain, indicating that the N-terminal part of MOG is extracellularly located. MOG comprises also two highly hydrophobic regions [6,16], HR1 and HR2, that could be potential membrane-spanning regions, suggesting that the C-terminus of MOG would face the extracellular space. To investigate the actual position of the different domains of MOG according to the membrane, we have used two MOG site-specific antibodies on cultured rat oligodendrocytes and on MOG-transfected CHO cells.…”

Section: Resultsmentioning

confidence: 99%

“…Specific anti-extracellular (anti-EC) domain antibodies were isolated from this polyclonal anti-MOG antiserum by affinity chromatography on a recombinant gluthatione S-transferase (GST)-Ig-like domain (amino acids 1Ϫ116) fusion-protein Sepharose column, prepared according to the manufacturer (Pharmacia). A synthetic 17-amino acid polypeptide corresponding to amino acids 202Ϫ 218 of MOG [6,17] was used to prepare a rabbit polyclonal antibody directed against the C-terminus of MOG. Specific Cterminal antibodies (anti-Cter) were purified on the same peptide coupled to a Sepharose column resin.…”

Section: Methodsmentioning

confidence: 99%

“…MOG sequence contains two major hydrophobic regions (designated as HR1 and HR2 in this paper), which are potentially arranged as A-helical transmembrane segments, thus leaving both the N-and C-termini of MOG in the extracellular space [6,16,19].…”

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confidence: 99%

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Membrane topology of the myelin/oligodendrocyte glycoprotein

Gaspera

Pham-Dinh

Roussel

et al. 1998

European Journal of Biochemistry

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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 membranespanning 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.Keywords : MOG; myelin; topology.Central nervous system myelin is synthesized as an extension of the oligodendrocyte plasma membrane, which wraps around axons in a concentric multilamellar sheath. Proteolipid proteins (PLP) and myelin basic proteins (MBP) are the most abundant components [1], accounting for about 80% of the protein. Myelin also contains minor glycoprotein components, such as myelin-associated glycoprotein (MAG) and myelin/oligodendrocyte glycoprotein (MOG).MOG was originally identified as the antigen recognized by the demyelinating antibodies present in serum of animals immunized with whole-brain homogenate [2] and was later characterized as a 26 kDa to 28-kDa glycoprotein [3]. Given its late expression during myelinogenesis in mammals [4Ϫ6] and its location at the membrane surface of oligodendrocytes and external lamellae of myelin sheaths [4,7], MOG has been proposed to play a role either in the completion and maintenance of myelin sheath [5,8], or in the adhesion of adjacent myelinated tracts [9]. However, in vivo and in vitro studies suggested that MOG may be a target autoantigen in autoimmune demyelinating diseases of the central nervous system. In animals with experimental autoimmune encephalomyelitis, an experimental model for multiple sclerosis, the injection of MOG peptides can initiate [12,13] and tolerization assays in a non-human primate model of experimental autoimmune encephalomyelitis led to a lethal encephalopathy [14]. The physiopathological mechanism responsible for this particular and deleterious effect of MOG humoral immunoreactivity may result from the fixation of a component of complement, C1q, to the extracellular domain of MOG [15].Sequence comparison of MOG cDNAs from rat, bovine, ...

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Section: Resultssupporting

confidence: 56%

Section: Resultsmentioning

confidence: 73%