Role of myelin-associated glycoprotein (siglec-4a) in the nervous system

Myelin-associated glycoprotein (MAG) is a 100 kDa glycoprotein located at the innermost layer of myelin sheets that remains in intimate contact with the axonal membrane. It is selectively expressed by myelinating cells including Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Due to its selective location and its effects on neurons, it was originally thought to be involved in axon-glia communication. The generation of MAG-deficient mice greatly expanded our knowledge about the physiological role of MAG, which helped to establish its critical roles in the normal formation and maintenance of myelinated axons. Interest in MAG was revived when it was described as the first myelin-derived inhibitor of axon regeneration. Since then numerous publications have provided detailed information about its axonal receptors and their signaling pathways. Recently, the nurture role of MAG on neurons was confirmed. On the other hand, MAG mediates signals coming from the axons that strongly impact on oligodendrocytes and Schwann cells, highlighting the bidirectional nature of axon-glia communication. Overall, MAG is a critical component of axon-glia interactions with multiple functions in the biology of both neurons and glial cells.