Mag
Developmental stage
In CNS isoform L-MAG is the major form synthesized early in development, and it persists as a significant proportion of the MAG present in the adult. In the PNS isoform L-MAG is expressed at modest levels during development; it is absent in the adult.
Domain
The C-terminal cytoplasmic region found only in isoform L-MAG is required for normal myelination in the central nervous system (CNS), but is apparently not required for normal myelination in the peripheral nervous system (PNS).
The extracellular domain is required to protect against axon degeneration (PubMed:19158290, PubMed:26335717). The first three Ig-like domains mediate interaction with RTN4R and RTN4RL2, but are not sufficient to inhibit neurite outgrowth (By similarity). The two C-terminal extracellular Ig-like C2-type domains are required for inhibition of axon longitudinal growth. Besides, the two C-terminal extracellular Ig-like C2-type domains are required for protection against apoptosis after nerve injury (PubMed:26335717).
Function
Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (PubMed:12089450, PubMed:27922006, PubMed:7533044). Not required for initial myelination, but seems to play a role in the maintenance of normal axon myelination (PubMed:10625334, PubMed:7516497, PubMed:9262180, PubMed:9469574, PubMed:9482781, PubMed:9482783). Protects motoneurons against apoptosis, also after injury; protection against apoptosis is probably mediated via interaction with neuronal RTN4R and RTN4RL2 (PubMed:26335717). Required to prevent degeneration of myelinated axons in adults; this probably depends on binding to gangliosides on the axon cell membrane (PubMed:15953602, PubMed:19158290). Negative regulator of neurite outgrowth that inhibits axon longitudinal growth (PubMed:12089450, PubMed:19158290, PubMed:27922006). Negative regulator of neurite outgrowth; in dorsal root ganglion neurons the inhibition is mediated primarily via binding to neuronal RTN4R or RTN4RL2 and to a lesser degree via binding to neuronal gangliosides (PubMed:17640868). In cerebellar granule cells the inhibition is mediated via binding to neuronal gangliosides (PubMed:17640868). In sensory neurons, inhibition of neurite extension depends only partially on RTN4R, RTN4RL2 and gangliosides (By similarity). Inhibits axon outgrowth by binding to RTN4R (PubMed:12089450). Preferentially binds to alpha-2,3-linked sialic acid (PubMed:27922006, PubMed:7533044). Binds ganglioside Gt1b (PubMed:27922006).
Post-translational modifications
N-glycosylated.
Phosphorylated on tyrosine residues.
Ubiquitinated, leading to proteasomal degradation.
Sequence Similarities
Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.
Tissue Specificity
Detected in the myelin tract in brain, especially in the corpus callosum and in peripheral nerve (PubMed:24191038, PubMed:7516497, PubMed:9482783). Expressed by myelinating glial cells in the central and peripheral nervous system (PubMed:10625334). Detected in oligodendrocyte processes before formation of compact myelin (PubMed:10625334, PubMed:2474006). Restricted to the periaxonal space after myelination (PubMed:10625334). Isoform S-MAG is the predominant isoform in CNS and PNS of the adult (at protein level) (PubMed:1716323).
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Membrane raft
Alternative names
Myelin-associated glycoprotein, Siglec-4a, Mag