Myelin-associated glycoprotein-mediated signaling in central nervous system pathophysiology.
The myelin-associated glycoprotein (MAG) is a type I membrane-spanning protein expressed exclusively in oligodendrocytes and Schwann cells. It has two generally known pathophysiological roles in the central nervous system (CNS): maintenance of myelin integrity and inhibition of CNS axonal regeneration. The subtle CNS phenotype resulting from genetic ablation of MAG expression has made mechanistic analysis of its functional role in these difficult. However, the past few years have brought some major revelations, particularly in terms of mechanisms of MAG signaling through the Nogo-66 receptor (NgR) complex. Although apparently converging through NgR, a readily noticeable fact is that the neuronal growth inhibitory effect of MAG differs from that of Nogo-66. This may result from the influence of coreceptors in the form of gangliosides or from MAG-specific neuronal receptors such as NgR2. MAG has several other neuronal binding partners, and some of these may modulate its interaction with the NgR complex or downstream signaling. This article discusses new findings in MAG-forward and -reverse signaling and its role in CNS pathophysiology.
Chen
Yanan
Y
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Aulia
Selina
S
Tang
Bor Luen
BL
D000818:Animals; D002493:Central Nervous System Diseases / Q000378:metabolism* / Q000503:physiopathology; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D009185:Myelin Proteins / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D006131:Growth Inhibitors; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; D020800:Receptor, Nerve Growth Factor