MAG gene expression

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Reaction [omitted]
Homo sapiens
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Myelin associated glycoprotein (MAG) is a low abundant component of the myelin sheath and is synthesized by oligodendrocytes and Schwann cells in the central and peripheral nervous system, respectively. MAG is also an adhesion molecule that binds to gangliosides and glycoproteins such as RTN4R and RTN4RL2 to mediate interaction between myelinating cells and neurons, and additionally functions after injury in the CNS to inhibit axon regeneration through the RHO A signaling pathway (reviewed in Schnarr and Lopez, 2009; Mehta et al, 2017; McKerracher and Rosen, 2015).
MAG expression is regulated in part by the binding of EGR2 and SOX10 to elements in the second intron of the gene (LeBlanc et al, 2007; Jang et al, 2006; Jones et al, 2007). Consistent with this, MAG expression is abrogated in EGR2-depleted mice and stimulated by ectopic EGR2 expression (Le et al, 2005; Nagarajan et al, 2001). At the protein level, MAG stability is postively regulated by the adhesion GPCR protein GPR98 (also known as VLGR1). GPR98 signals through G proteins, PKA and PKA to limit MAG ubiquitination and subsequent degradation, although the mechanism remains to be elucidated (Shin et al, 2013; reviewed in Mehta and Piao, 2017).

Literature References
PubMed ID Title Journal Year
24191038 Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C

Shin, D, Lin, ST, Fu, YH, Ptácek, LJ

Proc. Natl. Acad. Sci. U.S.A. 2013
27859941 Adhesion G-protein coupled receptors and extracellular matrix proteins: Roles in myelination and glial cell development

Mehta, P, Piao, X

Dev. Dyn. 2017
18634568 Interactions of Sox10 and Egr2 in myelin gene regulation

Jones, EA, Jang, SW, Mager, GM, Chang, LW, Srinivasan, R, Gokey, NG, Ward, RM, Nagarajan, R, Svaren, J

Neuron Glia Biol. 2007
15695336 Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination

Le, N, Nagarajan, R, Wang, JY, Araki, T, Schmidt, RE, Milbrandt, J

Proc. Natl. Acad. Sci. U.S.A. 2005
26441514 MAG, myelin and overcoming growth inhibition in the CNS

McKerracher, L, Rosen, KM

Front Mol Neurosci 2015
16923174 In vivo detection of Egr2 binding to target genes during peripheral nerve myelination

Jang, SW, Leblanc, SE, Roopra, A, Wrabetz, L, Svaren, J

J. Neurochem. 2006
11394999 EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression

Nagarajan, R, Svaren, J, Le, N, Araki, T, Watson, M, Milbrandt, J

Neuron 2001
17325040 Neuropathy-associated Egr2 mutants disrupt cooperative activation of myelin protein zero by Egr2 and Sox10

Leblanc, SE, Ward, RM, Svaren, J

Mol. Cell. Biol. 2007
19156870 Myelin-associated glycoprotein and its axonal receptors

Schnaar, RL, Lopez, PH

J. Neurosci. Res. 2009
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