Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MAG”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed1987

The amino acid sequences of the myelin-associated glycoproteins: homology to the immunoglobulin gene superfamily.

The myelin associated glycoproteins (MAG) are integral plasma membrane proteins which are found in oligodendrocytes and Schwann cells and are believed to mediate the axonal-glial interactions of myelination. In this paper we demonstrate the existence in central nervous system myelin of two MAG polypeptides with Mrs of 67,000 and 72,000 that we have designated small MAG (S-MAG) and large MAG (L-MAG), respectively. The complete amino acid sequence of L-MAG and a partial amino acid sequence of S-MAG have been deduced from the nucleotide sequences of corresponding cDNA clones isolated from a lambda gt11 rat brain expression library. Based on their amino acid sequences, we predict that both proteins have an identical membrane spanning segment and a large extracellular domain. The putative extracellular region contains an Arg-Gly-Asp sequence that may be involved in the interaction of these proteins with the axon. The extracellular portion of L-MAG also contains five segments of internal homology that resemble immunoglobulin domains, and are strikingly homologous to similar domains of the neural cell adhesion molecule and other members of the immunoglobulin gene superfamily. In addition, the two MAG proteins differ in the extent of their cytoplasmically disposed segments and appear to be the products of alternatively spliced mRNAs. Of considerable interest is the finding that the cytoplasmic domain of L-MAG, but not of S-MAG, contains an amino acid sequence that resembles the autophosphorylation site of the epidermal growth factor receptor.

Amino Acid Sequence↗
PubMed1989

The myelin-associated glycoprotein is enriched in multivesicular bodies and periaxonal membranes of actively myelinating oligodendrocytes.

The myelin-associated glycoprotein (MAG) is a member of the immunoglobulin gene superfamily that is selectively expressed by myelin-forming cells. A developmentally regulated, alternative splicing of a single MAG transcript produces two MAG polypeptides (72 and 67 kD) in the central nervous system (CNS). MAG occurs predominantly as the 67-kD polypeptide in the peripheral nervous system (PNS). This study determined the subcellular localization of CNS MAG at different postnatal times when the 72-kD form (7-d) and 67-kD form (adult) are quantitatively abundant. These distributions were also compared to those of MAG in the PNS. In adult rat, MAG is selectively enriched in periaxonal membranes of CNS myelin internodes. This restricted distribution differs from that in PNS myelin internodes where MAG is also enriched in paranodal loops, Schmidt-Lanterman incisures, and mesaxon membranes. In 7-d-old rat CNS, MAG was associated with periaxonal membranes during axonal ensheathment and enriched in Golgi membranes and cytoplasmic organelles having the appearance of multivesicular bodies (MVBs). MAG-enriched MVBs were found in oligodendrocyte perinuclear regions, in processes extending to myelin internodes, and along the myelin internode in outer tongue processes and paranodal loops. MAG-enriched MVBs were not found in oligodendrocytes from adult animals or in myelinating Schwann cells. These findings raise the possibility that the 72-kD MAG polypeptide is associated with receptor-mediated endocytosis of components from the periaxonal space or axolemma during active stages of myelination.

Aging↗
PubMed1997

Myelin-associated glycoprotein interacts with neurons via a sialic acid binding site at ARG118 and a distinct neurite inhibition site.

Inhibitory components in myelin are largely responsible for the lack of regeneration in the mammalian CNS. Myelin-associated glycoprotein (MAG), a sialic acid binding protein and a component of myelin, is a potent inhibitor of neurite outgrowth from a variety of neurons both in vitro and in vivo. Here, we show that MAG's sialic acid binding site is distinct from its neurite inhibitory activity. Alone, sialic acid-dependent binding of MAG to neurons is insufficient to effect inhibition of axonal growth. Thus, while soluble MAG-Fc (MAG extracellular domain fused to Fc), a truncated form of MAG-Fc missing Ig-domains 4 and 5, MAG(d1-3)-Fc, and another sialic acid binding protein, sialoadhesin, each bind to neurons in a sialic acid- dependent manner, only full-length MAG-Fc inhibits neurite outgrowth. These results suggest that a second site must exist on MAG which elicits this response. Consistent with this model, mutation of arginine 118 (R118) in MAG to either alanine or aspartate abolishes its sialic acid-dependent binding. However, when expressed at the surface of either CHO or Schwann cells, R118-mutated MAG retains the ability to inhibit axonal outgrowth. Hence, MAG has two recognition sites for neurons, the sialic acid binding site at R118 and a distinct inhibition site which is absent from the first three Ig domains.

Amino Acid Sequence↗
PubMed1984

Immunocytochemical studies of quaking mice support a role for the myelin-associated glycoprotein in forming and maintaining the periaxonal space and periaxonal cytoplasmic collar of myelinating Schwann cells.

The myelin-associated glycoprotein (MAG) is an integral membrane glycoprotein that is located in the periaxonal membrane of myelin-forming Schwann cells. On the basis of this localization, it has been hypothesized that MAG plays a structural role in (a) forming and maintaining contact between myelinating Schwann cells and the axon (the 12-14-nm periaxonal space) and (b) maintaining the Schwann cell periaxonal cytoplasmic collar of myelinated fibers. To test this hypothesis, we have determined the immunocytochemical localization of MAG in the L4 ventral roots from 11-mo-old quaking mice. These roots display various stages in the association of remyelinating Schwann cells with axons, and abnormalities including loss of the Schwann cell periaxonal cytoplasmic collar and dilation of the periaxonal space of myelinated fibers. Therefore, this mutant provides distinct opportunities to observe the relationships between MAG and (a) the formation of the periaxonal space during remyelination and (b) the maintenance of the periaxonal space and Schwann cell periaxonal cytoplasmic collar in myelinated fibers. During association of remyelinating Schwann cells and axons, MAG was detected in Schwann cell adaxonal membranes that apposed the axolemma by 12-14 nm. Schwann cell plasma membranes separated from the axolemma by distances greater than 12-14 nm did not react with MAG antiserum. MAG was present in adaxonal Schwann cell membranes that apposed the axolemma by 12-14 nm but only partially surrounded the axon and, therefore, may be actively involved in the ensheathment of axons by remyelinating Schwann cells. To test the dual role of MAG in maintaining the periaxonal space and Schwann cell periaxonal cytoplasmic collar of myelinated fibers, we determined the immunocytochemical localization of MAG in myelinated quaking fibers that displayed pathological alterations of these structures. Where Schwann cell periaxonal membranes were not stained by MAG antiserum, the cytoplasmic side of the periaxonal membrane was "fused" with the cytoplasmic side of the inner compact myelin lamella and formed a major dense line. This loss of MAG and the Schwann cell periaxonal cytoplasmic collar usually resulted in enlargement of the 12-14-nm periaxonal space and ruffling of the apposing axolemma. In myelinated fibers, there was a strict correlation between the presence of MAG in the Schwann cell periaxonal membrane and (a) maintenance of the 12-14-nm periaxonal space, and (b) presence of the Schwann cell periaxonal cytoplasmic collar.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Myelin-associated glycoprotein: electron microscopic immunocytochemical localization in compact developing and adult central nervous system myelin.

Light microscopic immunocytochemical studies have shown that myelin-associated glycoprotein (MAG) is localized in myelin of the developing CNS; but in the adult, MAG appears to be restricted to periaxonal regions of myelinated fibers. To extend these observations, we embedded optic nerves of 15-day-old rats, adult rats, and an adult human in epon after aldehyde and osmium tetroxide fixation. After 5% H2O2 pretreatment, thin sections were immunostained with 1:250-1:5,000 rabbit antiserum to rat CNS MAG according to the avidin-biotin-peroxidase complex (ABC) method. Dense deposits of reaction product covered compact myelin in both developing and adult optic nerves. When we used 1:500, 1:1,000, and 1:2,000 anti-MAG, less intense immunostaining of myelin was found. We also obtained the same localization in compact myelin with the peroxidase-antiperoxidase (PAP) method. With 1:250 anti-MAG, dense deposits of reaction product were not observed on axolemmal membranes or on oligodendroglial membranes located periaxonally and paranodally. In thin sections of adult human optic nerve, anti-MAG also stained compact myelin intensely. When thin sections of rat and human optic nerves were treated with preimmune or absorbed serum, no immunostaining was observed. Immunoblot tests showed that our MAG antisera did not react with any non-MAG myelin proteins. In contrast with earlier light microscopic data, this study shows that MAG localization does not change during CNS development; both developing and adult compact myelin sheaths contain MAG. As many biochemical studies also show that MAG is present in compact myelin, we suggest that this 100,000 dalton glycoprotein now be called myelin glycoprotein (MGP) instead of MAG.

Age Factors↗
PubMed1995

Abnormal expression and glycosylation of the large and small isoforms of myelin-associated glycoprotein in dysmyelinating quaking mutants.

The relative expression of large (L) and small (S) isoforms of the myelin-associated glycoprotein (MAG) and their glycosylation were compared in developing spinal cord of quaking and control mice. Using antisera specific for L- and S-MAG, respectively, it was shown that S-MAG is the principal isoform in quaking mice at all ages between 13 and 72 days, although L-MAG was just detectable by western blotting at the early ages. Both L- and S-MAG have higher apparent molecular weights in quaking mice than in controls. Experiments involving lectin binding and glycosidase treatment demonstrated that the higher molecular weight of MAG in the quaking mutant was due to a higher content of N-acetylneuraminic acid residues linked alpha 2-3 to galactose as well as to more branching of oligosaccharide moieties indicated by a higher content of subterminal galactose residues. The total sialic acid measured by HPAE-chromatography in purified quaking MAG was 40% higher than in control MAG. By contrast, quaking MAG contained less of the adhesion-related, HNK-1 carbohydrate epitope. Another difference was that a lower molecular weight form of MAG with predominantly high mannose oligosaccharides was prominent in young quaking mice, but not in controls. The abnormalities of MAG expression related to splicing of its mRNA and glycosylation may contribute to the myelin pathology in quaking mutants.

Amidohydrolases↗
PubMed2001

Anti-myelin associated glycoprotein antibodies: variability in patterns of IgM binding to peripheral nerve.

We previously found that serums with anti-sulfatide antibodies have several different patterns of binding to neural tissue. In this study, we asked whether serums with anti-myelin associated glycoprotein (MAG) antibodies also have similar variations in patterns of tissue binding. We examined binding to peripheral nerve in 49 serums with IgM anti-MAG antibodies and 13 serums with IgM anti-sulfoglucuronyl paragloboside (SGPG) antibodies but no MAG binding. We correlated patterns of binding with titers of IgM binding to MAG and SGPG measured by ELISA methods. Our results show that IgM in most anti-MAG serums stained areas of non-compact myelin, including the periaxonal and outer myelin membranes and Schmidt-Lanterman incisures. However, other patterns included IgM binding to areas of compact myelin and to non-myelin structures including axons and endoneurial macrophages. IgM in anti-SGPG serums bound to axons or macrophages, but rarely to myelin-related structures. A total of 11/62 (18%) of serums had IgM binding to axons, six with anti-MAG antibodies and five with anti-SGPG antibodies. The majority of these serums (73%) had SGPG titers greater than MAG titers when measured by ELISA. We conclude that anti-MAG serums have several different binding patterns to neural tissue, including axonal binding, especially when anti-MAG antibodies cross-react with SGPG. These different binding patterns may relate to the ability of anti-MAG serum IgM to bind both MAG and SGPG or to other molecules with a sulfated glucuronic acid epitope that are present in peripheral nerve.

Antibodies↗
PubMed1985

The species distribution of nervous system antigens that react with anti-myelin-associated glycoprotein antibodies.

The reactivity of monoclonal and polyclonal antibodies directed against human central nervous system (CNS) myelin-associated glycoprotein (MAG) was investigated in a number of animal species. The antibodies included mouse monoclonal antibodies obtained by immunization with human MAG; HNK-1, a mouse monoclonal antibody raised against a human lymphoblastoma and used to identify a subset of lymphocytes with natural killer function; human IgM paraproteins associated with neuropathy; and polyclonal antibodies obtained from rabbits immunized with rat or human MAG. Following polyacrylamide gel electrophoresis of CNS and peripheral nervous system (PNS) tissue from human, bovine, cat, rabbit, guinea pig, rat, mouse, frog, gold fish and chicken, proteins were electrophoretically transferred onto nitrocellulose. The immune-staining of electroblots showed distinct interspecies variation in the reactivity of the antibodies with MAG. In addition, the species distribution of several low molecular weight glycoproteins present in PNS tissue that cross-react with anti-MAG antibodies was determined. These low molecular weight antigens are not present in CNS homogenates or in purified human CNS myelin. It was also shown that IgM from a patient with peripheral neuropathy and paraproteinemia associated with anti-MAG antibodies recognized these low molecular weight antigens. The results suggest that IgM paraproteins, HNK-1 and some mouse monoclonal antibodies react with carbohydrate determinants shared by MAG and several lower molecular weight glycoproteins present only in human, bovine, cat and chicken PNS. Rabbit polyclonal anti-rat MAG antisera and mouse monoclonal antibodies reacting with peptide epitopes of MAG are much more specific for detecting MAG than antibodies reacting with carbohydrate epitopes of human MAG. The results are discussed in relation to human demyelinating peripheral neuropathy associated with IgM paraproteinemia.

Animals↗
PubMed2001

Brain gangliosides: functional ligands for myelin stability and the control of nerve regeneration.

Gangliosides, sialylated glycosphingolipids which are the predominant glycans on vertebrate nerve cell surfaces, are emerging as components of membrane rafts, where they can mediate important physiological functions. Myelin associated glycoprotein (MAG), a minor constituent of myelin, is a sialic acid binding lectin with two established physiological functions: it is involved in myelin-axon stability and cytoarchitecture, and controls nerve regeneration. MAG is found selectively on the myelin membranes directly apposed to the axon surface, where it has been proposed to mediate myelin-axon interactions. Although the nerve cell surface ligands for MAG remain to be established, evidence supports a functional role for sialylated glycoconjugates. Here we review recent studies that reflect on the role of gangliosides, sialylated glycosphingolipids, as functional MAG ligands. MAG binds to gangliosides with the terminal sequence 'NeuAc alpha 3Gal beta 3GalNAc' which is found on the major nerve gangliosides GD1a and GT1b. Gangliosides lacking that terminus (e.g., GM1 or GD1b), or having any biochemical modification of the terminal NeuAc residue fail to support MAG binding. Genetically engineered mice lacking the GalNAc transferase required for biosynthesis of the 'NeuAc alpha 3Gal beta 3GalNAc' terminus have grossly impaired myelination and progressive neurodegeneration. Notably the MAG level in these animals is dysregulated. Furthermore, removal of NeuAc residues from nerve cells reverses MAG-mediated inhibition of neuritogenesis, and neurons from mice lacking the 'NeuAc alpha 3 Gal beta 3GalNAc' terminus have an attenuated response to MAG. Cross-linking nerve cell surface gangliosides can mimic MAG-mediated inhibition of nerve regeneration. Taken together these observations implicate gangliosides as functional MAG ligands.

Animals↗
PubMed2001

Myelin-associated glycoprotein interacts with ganglioside GT1b. A mechanism for neurite outgrowth inhibition.

Myelin-associated glycoprotein (MAG) is expressed on myelinating glia and inhibits neurite outgrowth from post-natal neurons. MAG has a sialic acid binding site in its N-terminal domain and binds to specific sialylated glycans and gangliosides present on the surface of neurons, but the significance of these interactions in the effect of MAG on neurite outgrowth is unclear. Here we present evidence to suggest that recognition of sialylated glycans is essential for inhibition of neurite outgrowth by MAG. Arginine 118 on MAG is known to make a key contact with sialic acid. We show that mutation of this residue reduces the potency of MAG inhibitory activity but that residual activity is also a result of carbohydrate recognition. We then go on to investigate gangliosides GT1b and GD1a as candidate MAG receptors. We show that MAG specifically binds both gangliosides and that both are expressed on the surface of MAG-responsive neurons. Furthermore, antibody cross-linking of cell surface GT1b, but not GD1a, mimics the effect of MAG, in that neurite outgrowth is inhibited through activation of Rho kinase. These data strongly suggest that interaction with GT1b on the neuronal cell surface is a potential mechanism for inhibition of neurite outgrowth by MAG.

Animals↗
PubMed2006

Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti-myelin-associated glycoprotein antibody.

Axonal injury is a hallmark of traumatic brain injury (TBI) and is associated with a poor clinical outcome. Following central nervous system injury, axons regenerate poorly, in part due to the presence of molecules associated with myelin that inhibit axonal outgrowth, including myelin-associated glycoprotein (MAG). The involvement of MAG in neurobehavioral deficits and tissue loss following experimental TBI remains unexplored and was evaluated in the current study using an MAG-specific monoclonal antibody (mAb). Anesthetized rats (n=102) were subjected to either lateral fluid percussion brain injury (n=59) or sham injury (n=43). In surviving animals, beginning at 1 h post-injury, 8.64 microg anti-MAG mAb (n=33 injured, n=21 sham) or control IgG (n=26 injured, n=22 sham) was infused intracerebroventricularly for 72 h. One group of these rats (n=14 sham, n=11 injured) was killed at 72 h post-injury for verification of drug diffusion and MAG immunohistochemistry. All other animals were evaluated up to 8 weeks post-injury using tests for neurologic motor, sensory and cognitive function. Hemispheric tissue loss was also evaluated at 8 weeks post-injury. At 72 h post-injury, increased immunoreactivity for MAG was seen in the ipsilateral cortex, thalamus and hippocampus of brain-injured animals, and anti-MAG mAb was detectable in the hippocampus, fimbria and ventricles. Brain-injured animals receiving anti-MAG mAb showed significantly improved recovery of sensorimotor function at 6 and 8 weeks (P<0.01) post-injury when compared with brain-injured IgG-treated animals. Additionally, at 8 weeks post-injury, the anti-MAG mAb-treated brain-injured animals demonstrated significantly improved cognitive function and reduced hemispheric tissue loss (P<0.05) when compared with their brain-injured controls. These results indicate that MAG may contribute to the pathophysiology of experimental TBI and treatment strategies that target MAG may be suitable for further evaluation.

Animals↗
PubMed1990

The large isoform of myelin-associated glycoprotein is scarcely expressed in the quaking mouse brain.

Two polypeptide isoforms of myelin-associated glycoprotein (MAG) with molecular masses of 72 and 67 kDa are produced by alternative splicing of the exon 12 portion. Our previous work has demonstrated that in the quaking mouse brain this alternative splicing is lacking and that the mRNA coding the large MAG isoform (L-MAG) is scarcely expressed, whereas that of small MAG isoform (S-MAG) is overexpressed. In the present study, we prepared antisera specific to the S-MAG and L-MAG amino acid residues, respectively. Immunoblots showed that the L-MAG band was scarcely detectable in the quaking mouse brain, whereas the S-MAG band had an apparently higher molecular mass than in the normal control. Our immunohistochemical study also showed that L-MAG was scarcely stained in the quaking mouse brain. These results seemed to reflect a reduction in content of L-MAG mRNA and abnormal glycosylation in the quaking mouse brain.

Animals↗
PubMed1987

Antibodies against denatured and reduced thyroid microsomal antigen in autoimmune thyroid disease.

Different antigenic determinants on thyroid microsomal antigen (MAg) could induce different antibodies, which, in turn, could have differing importance in the pathogenesis of autoimmune thyroid disease. In this study we demonstrated three types of microsomal antibodies (MAbs) present in serum of patients with autoimmune thyroid disease by Western blot analysis. These MAbs reacted with native, denatured, and denatured and reduced MAg. Methods for detecting the MAbs were developed, and the clinical significance of these Abs was analyzed in 197 patients with thyroid disorders. For measurement of Ab against native and denatured MAg, an enzyme-linked immunosorbent assay, in which wells were coated with untreated or sodium dodecyl sulfate-denatured MAg, was used. For measurement of Ab against denatured and reduced MAg, 6% SDS-polyacrylamide gel electrophoresis followed by Western blot analysis was used. Native MAb enzyme-linked immunosorbent assay values correlated highly with microsomal hemagglutination titers, but patients with high titers of Ab against native MAg did not necessarily have Ab against denatured MAg or reduced MAg. Abs against denatured MAg or denatured and reduced MAg were found in patients with Hashimoto's disease (28.8% and 13.6%) and Graves' disease (22.4% and 11.2%). The percentage of patients with positive denatured and reduced MAb was higher in Graves' disease patients who had a longer sick interval or who developed hypothyroidism after radioiodine treatment. This study provides the first clear demonstration that MAbs are heterogeneous. The data suggest that antibodies against denatured or denatured and reduced MAg may be related to destruction of the thyroid gland.

Autoantibodies↗
PubMed2005

The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein.

The Nogo-66 receptor (NgR1) is a promiscuous receptor for the myelin inhibitory proteins Nogo/Nogo-66, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp). NgR1, an axonal glycoprotein, is the founding member of a protein family composed of the structurally related molecules NgR1, NgR2, and NgR3. Here we show that NgR2 is a novel receptor for MAG and acts selectively to mediate MAG inhibitory responses. MAG binds NgR2 directly and with greater affinity than NgR1. In neurons NgR1 and NgR2 support MAG binding in a sialic acid-dependent Vibrio cholerae neuraminidase-sensitive manner. Forced expression of NgR2 is sufficient to impart MAG inhibition to neonatal sensory neurons. Soluble NgR2 has MAG antagonistic capacity and promotes neuronal growth on MAG and CNS myelin substrate in vitro. Structural studies have revealed that the NgR2 leucine-rich repeat cluster and the NgR2 "unique" domain are necessary for high-affinity MAG binding. Consistent with its role as a neuronal MAG receptor, NgR2 is an axonassociated glycoprotein. In postnatal brain NgR1 and NgR2 are strongly enriched in Triton X-100-insoluble lipid rafts. Neural expression studies of NgR1 and NgR2 have revealed broad and overlapping, yet distinct, distribution in the mature CNS. Taken together, our studies identify NgRs as a family of receptors (or components of receptors) for myelin inhibitors and provide insights into how interactions between MAG and members of the Nogo receptor family function to coordinate myelin inhibitory responses.

Animals↗
PubMed1989

Anti-myelin-associated glycoprotein IgM antibody titers in neuropathy associated with macroglobulinemia.

Twenty-seven patients with neuropathy and IgM monoclonal gammopathy were tested for antigen specificity of the M-protein and for anti-myelin-associated glycoprotein (MAG) IgM levels by immunoblot. In 16 patients (59.2%) the M-protein reacted with MAG and with cross-reactive glycoconjugates. Anti-MAG IgM titers in these patients ranged between 1:12,800 and 1:100,000. A fainter IgM reactivity with MAG and related glycoconjugates was detected in 3 additional patients with neuropathy, but also in 8 of 24 patients with IgM M-protein without neuropathy (33.3%). This reactivity was not due to the M-protein and corresponded to antibody titers of 1:400 or less in all but 1 patient with a titer of 1:3,200. Low titers of anti-MAG IgM (1:200 or less) were also detected in 17 of 101 control patients without IgM M-proteins (16.8%), while 1 patient with neuropathy of unknown cause had anti-MAG IgMK titers of 1:25,600. In 1 patient with neuropathy and IgM M-protein that was not anti-MAG, the M-protein bound to other antigens in nerve, while in 6, other possible causes or mechanisms for the neuropathy were found. In this study, high titers of anti-MAG IgM antibodies were always associated with neuropathy. The presence of low levels of anti-MAG IgM in a significant proportion of controls suggests that monoclonal expansion of naturally occurring B-cell clones secreting anti-MAG IgM may be responsible for the high incidence of this antigen specificity of the M-protein.

Adult↗
PubMed1989

Evidence for an early role for myelin-associated glycoprotein in the process of myelination.

The expression of myelin-associated glycoprotein (MAG) in purified rat Schwann cells following coculture with dorsal root ganglion neurons was compared with the expression of galactocerebroside (GalC) and Po using immunocytochemistry. In defined serum-free medium, lacking ascorbic acid, in which Schwann cells proliferate but neither ensheathe nor myelinate axons, axonal interaction up-regulated the cell surface expression of MAG and GalC but not of Po. Excision of neuronal cell bodies resulted in a down-regulation of both MAG and GalC from the Schwann cell surface. When cocultures were switched to complete medium (serum plus ascorbic acid) to promote myelination, Schwann cells committed to form myelin continued to express high levels of MAG and GalC on their surface, but nonmyelinating Schwann cells down-regulated MAG and GalC. There was significant MAG immunoreactivity associated with the external aspect of the apparent nodal region of developing myelin sheaths. Permeabilization prior to immunostaining revealed that all of the Schwann cell cytoplasmic processes of nascent internodes were significantly stained with anti-MAG antibodies before the appearance of Po immunoreactivity. The amount of MAG on the surface of mature myelin segments was reduced compared with developing myelin segments, but there was a considerable amount of anti-MAG staining in the paranodes and Schmidt-Lanterman incisures. The time of expression and localization of MAG indicates that it may be a critical molecule in the process by which the Schwann cell engulfs an axon destined to be myelinated and establishes the extent of the future internode.

Animals↗
PubMed1987

Characterization of binding properties of the myelin-associated glycoprotein to extracellular matrix constituents.

The myelin-associated glycoprotein (MAG) can be obtained from adult mouse brain from detergent-lysates of a crude membrane fraction as a 96-100 kd form (detergent solubilized MAG), and from 100,000 g supernatants of homogenates as a 90-96 kd form (soluble MAG). The soluble form distributes into the Triton X-114-poor aqueous phase, while detergent-solubilized MAG predominantly enters the Triton X-114-rich phase. Both molecular forms bind to heparin in hypo- and isotonic buffers. Soluble MAG binds to several collagens (type G, I, II, III, IV, V, VI, IX) with a kd of 5.7 X 10(-8) M for collagen type IX and 2.0 X 10(-7) for collagen type IV. Binding of 125I-labeled MAG to collagen G can be completely inhibited by unlabeled MAG and collagen G, but not by heat-denatured collagen. MAG does not bind to itself, laminin, fibronectin, or the neural cell adhesion molecules L1 and N-CAM. Binding of MAG to collagen G is most effectively blocked by a high molecular weight dextran sulfate, heparan sulfate and heparin, with chondroitin sulfate and a low molecular weight dextran sulfate being less potent blockers. These findings are in agreement with previous observations on the localization of MAG in basal lamina and interstitial collagens of the sciatic nerve in situ.

Animals↗
PubMed1991

Cell adhesion properties of myelin-associated glycoprotein in L cell fibroblasts.

Myelin-associated glycoprotein (MAG) is a cell surface molecule expressed by oligodendrocytes and Schwann cells. In order to determine whether MAG expression can confer adhesive properties to cells which normally do not aggregate in suspension, the cDNA encoding the long form of MAG (L-MAG) was introduced into L cell fibroblasts by retroviral infection. Clonal L cell lines expressing MAG were then subjected to a cell aggregation assay. Our results indicate that L-MAG can function as an intercellular adhesion molecule in a heterologous cell system. A critical threshold value of L-MAG expression was required for cell aggregation to occur. The adhesive properties of these cells were specific to MAG, since monoclonal antibodies directed against its extracellular domain inhibited aggregation. Furthermore, the adhesion was found to be calcium- and temperature-independent. Cell sorting experiments demonstrated that L-MAG-expressing cells bind in a heterotypic fashion to parental L cell fibroblasts. These results suggest that L-MAG can function as a heterotypic cell adhesion molecule recognizing a cell surface molecule(s) expressed by L cells.

Animals↗