Disease relevance of Mag

• Relapsing lesions, characterized by demyelination of areas previously remyelinated by Schwann cells, were studied for differences in the distribution of P0 and MAG [1].
• Schwann cells infected with a recombinant retrovirus expressing myelin-associated glycoprotein antisense RNA do not form myelin [2].
• From this sequence it may be deduced that L1 and N-CAM are involved in fasciculation, initial axon-Schwann cell interaction, and onset of myelination, with MAG to follow and MBP to appear only in compacted myelin [3].
• Here, we show, first, that a soluble, chimeric form of MAG (MAG-Fc), when secreted from CHO cells in a collagen gel and hence in the absence of a fixed substrate, inhibits/deflects neurite outgrowth from P6 dorsal root ganglion (DRG) neurons [4].
• Myelin-associated glycoprotein shares an antigenic determinant with a glycoprotein of human melanoma cells [5].

Psychiatry related information on Mag

• Despite their motor deficits, Mag- and Galgt1-null mice demonstrated hyperactivity, with spontaneous locomotor activity significantly above that of wild type mice [6].

High impact information on Mag

• Crosslinking of large MAG with antibody induces a rapid increase in the specific activity of Fyn kinase [7].
• In Krox-20-/- mice, Schwann cells wrap their cytoplasmic processes only one and a half turns around the axon, and although they express the early myelin marker, myelin-associated glycoprotein, late myelin gene products are absent, including those for protein zero and myelin basic protein [8].
• Our findings do not support the widely held view that MAG is critical for myelin formation but rather indicate that MAG is necessary for maintenance of the cytoplasmic collar and periaxonal space of myelinated fibres [9].
• The hypothesis that myelin-associated glycoprotein (MAG) initiates myelin formation is based in part on observations that MAG has an adhesive role in interactions between oligodendrocytes and neurons [9].
• Furthermore, the over- or underexpression of MAG in transfected Schwann cells in vitro leads to accelerated myelination or hypomyelination, respectively [9].

Chemical compound and disease context of Mag

• Expression of the two forms of MAG mRNA was studied here in experimentally introduced demyelination and remyelination by Cuprizone intoxication [10].

Biological context of Mag

• Absence of MAG was correlated with reduced axonal calibers, decreased neurofilament spacing, and reduced neurofilament phosphorylation [11].
• Binding of soluble myelin-associated glycoprotein to specific gangliosides induces the association of p75NTR to lipid rafts and signal transduction [12].
• Analysis of a panel of interspecies somatic cell hybrids indicated that all MAG coding sequences reside on chromosome 7 [13].
• Following the inheritance of a restriction fragment length polymorphism associated with MAG coding sequences allowed the locus to be positioned 0.5 centimorgans from the locus Abpa (androgen binding protein alpha) on proximal chromosome 7 [13].
• A small fraction of the MAG and MOG extracted from oligodendrocytes partitioned into the aqueous phase, suggesting an altered conformation outside myelin or a different state of glycosylation [14].

Anatomical context of Mag

• The increased synthesis of MAG and Wolfgram protein, two proteins present in uncompacted myelin sheath and paranodal loops, was demonstrated by high levels of messengers [15].
• Furthermore, the fine structure of mld oligodendrocytes was normal and the MAG immunostaining was similar to age-matched controls [15].
• Sodium channel clustering and node of Ranvier frequency were studied in whole-mount sciatic nerves with sodium channel and MAG antibodies [16].
• Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons [12].
• Myelin-associated glycoprotein in the central and peripheral nervous system of quaking mice [17].

Associations of Mag with chemical compounds

• Myelin-associated glycoprotein (MAG), a minor constituent of central and peripheral nervous system myelin, is a member of the Siglec family of sialic acid-binding lectins and binds to gangliosides GD1a and GT1b, prominent molecules on the axon surface [6].
• Here we report that Fyn tyrosine kinase is activated during the initial stages of myelination and that it is associated with the large myelin-associated glycoprotein (MAG), an adhesion molecule that has been implicated in myelinogenesis [7].
• Steady-state levels of mRNA for myelin-associated glycoprotein, myelin basic protein, and ceramide galactosyltransferase were already profoundly depressed after 1 week of Cuprizone exposure and were only 10-20% of control values after 2 weeks [18].
• Furthermore, two ligands of CSL, the myelin-associated glycoprotein and an axonal glycoprotein, with a relative molecular mass of 31 kDa, were not decreased in level in the purified myelin fraction isolated from mld mice [19].
• Basigin was found to bind to high mannose-carrying cell recognition molecules, such as myelin-associated glycoprotein, L1, the beta2-subunit of Na+/K+-ATPase and an oligomannosidic neoglycolipid [20].

Enzymatic interactions of Mag

• Myelin-associated glycoprotein was seen periaxonally in both normal myelin sheaths and sheaths which showed extensive splitting and ballooning as seen with toluidine blue stain and myelin basic protein antiserum [21].

Regulatory relationships of Mag

• We show that MAG-deficient Schwann cells do myelinate DRG neurons in vitro and express the myelin-specific glycolipid galactocerebroside (Gal-C) and the myelin proteins P0 and MBP [22].
• GFAP-positive cells in the presence of fetal calf serum very rarely expressed the myelin associated glycoprotein (MAG) or O1, both of which are expressed on more differentiated oligodendrocytes, and never expressed O10 that is characteristic of even more mature oligodendrocytes [23].

Other interactions of Mag

• Furthermore, the developmental change between the two molecular forms of MAG (p72MAG/p67MAG) was delayed in mld mice [15].
• Myelin-associated glycoprotein and other proteins in Trembler mice [24].
• Immunoblotting analysis did not reveal an increased apparent Mr for MAG in the Jimpy mouse, as has been observed in some other hypomyelinating murine mutants [25].
• No abnormal accumulation of MAG, MBP, or CNP in the cell body was found [26].
• In the current studies, CNS and PNS histopathology and behavior of Mag-null, Galgt1-null, and double-null mice were compared on the same mouse strain background [6].

Analytical, diagnostic and therapeutic context of Mag

• Immunoblotting analysis did not reveal an increased apparent Mr for MAG, as has been observed in quaking and trembler mice [27].
• Furthermore, at 8 weeks of age, single fiber preparation and electron microscopy revealed that the number of profiles indicative of degeneration was substantially increased in MAG-/N-CAM- mutants when compared to MAG- mice [28].
• 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 continue to express S-MAG [29].
• These results demonstrate that MAG expression is regulated in response to cortical axotomy, and indicate that it may limit axonal regeneration after CNS injury [30].
• 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 [31].

References