The amino acid sequences of the myelin-associated glycoproteins: homology to the immunoglobulin gene superfamily (original) (raw)
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Structure and Function of the Myelin-Associated Glycoproteins
Annals of the New York Academy of Sciences, 1990
Axons exhibit complex, reciprocal interactions with myelinating glial cells, that is, Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Contact with the axon regulates the proliferation of these glial cells and determines their state of differentiation, most dramatically their elaboration and maintenance of the myelin sheath. The glial cell, in turn, influences both the topographic segregation of axonal membrane constituents and the diameter of the adjacent axonal segment. These axonal-glial interactions are essential for the formation of a mature, fully differentiated myelinated nerve fiber, an essential component of the vertebrate nervous system.'
Structure and Function of the Myelin‐Associated Glycoproteinsa
Annals of the New York Academy of Sciences, 1990
Axons exhibit complex, reciprocal interactions with myelinating glial cells, that is, Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Contact with the axon regulates the proliferation of these glial cells and determines their state of differentiation, most dramatically their elaboration and maintenance of the myelin sheath. The glial cell, in turn, influences both the topographic segregation of axonal membrane constituents and the diameter of the adjacent axonal segment. These axonal-glial interactions are essential for the formation of a mature, fully differentiated myelinated nerve fiber, an essential component of the vertebrate nervous system.' This intimate functional interrelationship is, in turn, reflected in the close apposition of the respective plasma membranes of the axon and the myelinating glial cell. These membranes are separated by a regular extracellular space of 120-140 angstroms that is actively maintained even in pathologic conditions.2 The panoply of cell surface proteins present on the apposed membranes is likely to mediate these cellular interactions as well as maintain the periaxonal space. In addition, as they are extracellularly disposed, these proteins are potential targets in viral and immune-mediated damage to myelinated fibers. Identification and characterization of these membrane constituents should therefore provide important insights into the molecular mechanisms of these cell-cell interactions and into the pathogenesis of demyelinating diseases such as multiple sclerosis. Of the currently identified cell surface constituents of myelinating glial cells, the myelin-associated glycoproteins (MAG proteins) are the most likely candidates for mediating this interaction. These proteins are integral membrane proteins that are minor constiuents of the myelin sheath, comprising about 1% of the total protein content of CNS myelin and less than one tenth of that in PNS ~n y e l i n .~ Unlike structural components of compact myelin, such as the basic proteins or the proteolipid protein, the MAG proteins are present in noncompacted myelin membranes on the basis of fractionation studies as well as immuno-0 These studies were aided by basic research grant No.
Molecular cloning and primary structure of myelin-associated glycoprotein
Proceedings of the National Academy of Sciences, 1987
Myelin-associated glycoprotein (MAG) may play a role in the cellular interactions leading to myelination. Using monoclonal antibodies and conventional antisera against MAG, we have isolated a cDNA clone from an expression library prepared from rat brain mRNA. The identity of the clone was confirmed by the exact match between its nucleotide sequence and two peptide sequences of 13 and 9 amino acids that we obtained by Edman degradation of two CNBr fragments of MAG. The cDNA clone hybridized to two size species of mRNA in rat approximately 3.5 kilobases in length. These mRNAs were present in brain but not liver and were expressed most abundantly at the time of active myelination (day 14). The mRNA for MAG was present at barely detectable levels in hypomyelinating jimpy mice compared to normal littermate controls. Therefore the MAG cDNA clone is both brain and myelin specific. DNA sequence analysis revealed that our MAG cDNA was derived from the same mRNA as clone plB236, a randomly selected, brain-specific, partial cDNA isolated by Sutcliffe etal. Analysis of the predicted protein sequence suggests that MAG has a long extracellular domain (499 amino acids), followed by a short transmembrane segment (20 amino acids) and an intracellular carboxyl-terminal domain (90 amino acids). The molecule has several glycosylation sites, three internal repeats homologous to a repeat in the neural cell adhesion molecule (N-CAM), and sites for phosphorylation near the carboxyl terminus. The primary structure reported here provides a molecular framework for further investigations into the function of the MAG molecule.
Organization of Myelin Protein Genes: Myelin-Associated Glycoprotein
Annals of the New York Academy of Sciences, 1990
Myelinogenesis requires an orchestrated series of cellular events to generate and compact concentric layers of the oligodendrocyte or Schwann cell membrane around an axon. The regulation and modulation of interactions between cell membranes and between adjacent cell surfaces have particular importance in the elaboration of the myelin sheath. The myelin component myelin-associated glycoprotein (MAG) has been implicated as a key molecule in cell-cell interactions during myelinogenesis.1*2 The potential function of MAG as a cell adhesion molecule is also indicated by studies of cell adhesion in uitro3 as well as by its structural resemblance to more defined cell adhesion molecules such as N-CAM. This article reviews our studies on the structure and genetics of MAG.
The Journal of Neuroscience, 1998
The myelin-associated glycoprotein (MAG) is a member of the immunoglobulin gene superfamily and is thought to play a critical role in the interaction of myelinating glial cells with the axon. Myelin from mutant mice incapable of expressing MAG displays various subtle abnormalities in the CNS and degenerates with age in the peripheral nervous system (PNS). Two distinct isoforms, large MAG (L-MAG) and small MAG (S-MAG), are produced through the alternative splicing of the primary MAG transcript. The cytoplasmic domain of L-MAG contains a unique phosphorylation site and has been shown to associate with the fyn tyrosine kinase. Moreover, L-MAG is expressed abundantly early in the myelination process, possibly indicating an important role in the initial stages of myelination. We have adapted the gene-targeting approach in embryonic stem cells to generate mutant mice that express a truncated form of the L-MAG isoform, eliminating the unique portion of its cytoplasmic domain, but that cont...
Isolation and sequence of a cDNA encoding the major structural protein of peripheral myelin
Cell, 1985
The myelin sheath is a multilayered membrane, unique to the nervous system, which functionsas an insulator to increase greatly the velocity of axonal impulse conduction. We have used the techniques of differential screening and hybrid selection to identify a cDNA clone encoding the Schwann cell glycoprotein P,, the major structural protein of the peripheral myelin sheath. The sequence of this protein, deduced from the nucleotide sequence of the cloned cDNA, indicates that PO is an integral membrane protein containing a single membrane-spanning region, a large hydrophobic extracellular domain, and a smaller basic intracellular domain. The structure of the protein suggests that each of these domains plays an essential role in generating the highly ordered structure of the myelin sheath. Furthermore, we find that the induction of P, mRNA coincides with the initiation of myelin formation, and we propose a model in which the glycoprotein serves as a molecular guidepost for this process.
Molecular and Cellular Neuroscience, 2006
The two myelin-associated glycoprotein (MAG) isoforms are cell adhesion molecules that differ only in their cytoplasmic domains, but their specific roles are not well understood. In this study, we present a transgenic mouse line that specifically expresses GFP-tagged S-MAG correctly regulated and targeted into the myelin sheath allowing the specific discrimination of L-and S-MAG on the subcellular level. Here, we describe the differential expression pattern and spatial distribution of L-and S-MAG during development as well as in the adult central and peripheral nervous system. In peripheral nerves, where S-MAG is the sole isoform, we observed S-MAG concentrated in different ring-like structures such as periaxonal and abaxonal rings, and discs spanning through the compact myelin sheath perpendicular to the axon. In summary, our data provide new insight in the subcellular distribution of the two isoforms fundamental for the understanding of their specific functions in myelin formation and maintenance. D
Journal of Cell Biology, 1990
The myelin-associated glycoproteins (MAG) are members of the immunoglobulin gene superfamily that function in the cell interactions of myelinating glial cells with axons. In this paper, we have characterized the structural features of these proteins. The disposition of MAG in the bilayer as a type 1 integral membrane protein (with an extracellularly disposed amino terminus, single transmembrane segment, and cytoplasmic carboxy terminus) was demonstrated in protease protection studies of MAG cotranslationally inserted into microsomes in vitro and in immunofluorescent studies with site specific antibodies. A genetically engineered MAG cDNA, which lacks the putative membrane spanning segment, was constructed and shown to encode a secreted protein.
Characterization and Expression of the cDNA Coding for the Human Myelin/Oligodendrocyte Glycoprotein
Journal of Neurochemistry, 2002
Abstract: We report here the characterization of a full-length cDNA encoding the human myelin/oligodendrocyte glycoprotein (MOG). The sequence of the coding region of the human MOG cDNA is highly homologous to that of other previously cloned mouse, rat, and bovine MOG cDNAs, but the 3′ untranslated region differs by an insertion of an Alu sequence between nucleotides 1,590 and 1,924. Accordingly, northern blot analyzes with cDNA probes corresponding to the coding region or the 3′ untranslated Alu-containing sequence revealed a single band of 2 kb, rather than the 1.6 kb of bovine, rat, or mouse MOG cDNA(s). Immunocytochemical analysis of HeLa cells transfected with human MOG cDNA, which was performed using a specific antibody raised against whole MOG, clearly indicated that MOG is expressed at the cell surface as an intrinsic protein. These data are in accordance with the predicted amino acid sequence, which contains a signal peptide and two putative transmembrane domains. The knowledge of the human MOG sequence should facilitate further investigations on its potential as a target antigen in autoimmune demyelinating diseases like multiple sclerosis.