Myelin-associated glycoprotein (MAG, Siglec-4) is a type 1

transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

localized in periaxonal Schwann cell and oligodendrocyte membranes, where it plays a role in glial-axonal interactions. MAG is a member of the SIGLEC family of proteins and is a functional ligand of the NOGO-66 receptor, NgR. MAG is believed to be involved in

myelination Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...

during

nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...

regeneration in the PNS and is vital for the long-term survival of the myelinated axons following

myelinogenesis Myelinogenesis is the formation and development of myelin sheaths in the nervous system, typically initiated in late prenatal neurodevelopment and continuing throughout postnatal development. Myelinogenesis continues throughout the lifespan to ...

. In the CNS MAG is one of three main myelin-associated inhibitors of axonal regeneration after injury, making it an important protein for future research on neurogenesis in the CNS.

Structure

MAG is a 100 kDA glycoprotein. Uncleaved MAG is a complete transmembrane form, which acts as a signaling and adhesion molecule. MAG can also act as a signaling molecule as a soluble protein after it has been proteolytically shed. This form of the protein is called dMAG.

Adhesion

MAG has an extended conformation of five immunoglobulin (Ig) domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. MAG-oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1.

Function

Myelin-axon interactions

MAG is a critical protein in the formation and maintenance of myelin sheaths. MAG is localized on the inner membrane of the myelin sheath and interacts with axonal membrane proteins to attach the myelin sheath to the axon..\ Mutations to the MAG gene are implicated in demyelination diseases such as multiple sclerosis.

Inhibition of nerve regeneration

Axons in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

do not regenerate after injury the same way that axons in the

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...

do. The mechanism responsible for inhibited

neuroregeneration Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system ...

is regulated by three main proteins, one of which is MAG. The exact mechanism through which MAG inhibits neuroregeneration appears to be through binding of NgR. This receptor is also bound by Nogo protein, suggesting that the mechanism of myelin-associated inhibition of axon regeneration through NgR the has redundant ligands, furthering the inhibition. MAG binds with high affinity to NgR, suggesting that it is equally as responsible for inhibition of axon regeneration as Nogo.

Rho kinase pathway

Once MAG (or Nogo) has bound to NgR, NgR activates the rho kinase (ROCK) pathway. The activation of the rho kinase pathway leads to the phosphorylation of proteins which inhibit neurite outgrowth.

External links

References

Lectins SIGLEC {{gene-19-stub