Neural Protein 1B236/Myelin‐Associated Glycoprotein (MAG) Defines a Subgroup of the Immunoglobulin Superfamily

Abstract

We have reviewed the structure and properties of the neural protein 1B236/MAG. This molecule consists largely of five Ig-like domains separated from its carboxyl terminal tail by a single membrane-spanning region. Two forms of the protein differ in the length and sequence of the carboxyl terminus: these are encoded by alternatively spliced mRNAs that are differentially expressed during postnatal neural development. The Ig-like domains of 1B236/MAG are unusual in having structural similarities to Ig V domains but with short Cys-Cys distances characteristic of C domains. Several other Ig-like molecules exhibit this structural feature, including the cell adhesion molecule N-CAM, which is most closely related in sequence to 1B236/MAG. We have proposed 1B236/MAG as the prototype for this subgroup of the Ig family and offer a model for this type of Ig domain structure. 1B236/MAG probably acts as a cell adhesion molecule to mediate interactions between cells in a fashion similar to that proposed for N-CAM. In particular, 1B236/MAG may be involved in interactions between myelinating oligodendrocytes or Schwann cells and axons or between adjacent layers of myelin membrane during the process of myelin compaction. It is most likely that the homophilic or heterophilic interactions of 1B236/MAG occur through binding to the Ig-like domains. The structure of 1B236/MAG is therefore quite consistent with its proposed function and may serve as the model for this class of cell-cell interaction molecules. One would predict, for example, that the neuron-glia cell adhesion molecule Ng-CAM, also known as NILE or L1 (Bock et al. 1985, Friedlander et al. 1985), which mediates interactions between neurons and glial cells, would have a very similar structure to those of N-CAM and 1B236/MAG. In addition, the carboxyl terminal tails of the 1B236/MAG proteins may also be involved in interactions with cytoskeletal components, during membrane vesicle transport through the glial cytoplasm during myelination or through neuronal axoplasm or cytoplasm. The availability of full-length cDNA clones of 1B236/MAG mRNAs with the ability to express these products in vitro will enable the structure and interactions of 1B236/MAG to be tested in detail.

The myelin-associated glycoprotein is enriched in multivesicular bodies and periaxonal membranes of actively myelinating oligodendrocytes.

“…This function was first proposed on the basis of MAG's biochemical properties and enrichment in myelin subfractions (21,22). This hypothesis was subsequently supported by several immunocytochemical studies, which demonstrated MAG's enrichment in periaxonal regions of central nervous system (CNS) and peripheral nervous system (PNS) myelin internodes (28), and which showed a strict correlation between the presence of MAG in periaxonal membranes and the formation and maintenance of the periaxonal space during Schwann cell remyelination in Quaking mice (33,35).Several laboratories have deduced the amino acid sequence ofCNS MAG from cDNA clones (1,14,15,26) and have identified MAG as a member of the immunoglobulin gene superfamily (37). Amino acid sequence homologies between the extracellular domains of MAG and those of other 1.…”

Myelin-Associated Glycoprotein Gene Expression in the Presence and Absence of Schwann Cell-Axonal Contact

“…MAG is a minor component of both CNS and PNS myelin, comprising approximately 0.1 % of the total myelin proteins in the PNS [for review see, 15,16]. The completely gly cosylated protein contains approximately 30% carbohydrate in a covalent linkage and has an apparent molecular weight of approx imately 100 kD.…”

The mouse neuronal cell surface protein F3: a phosphatidylinositol-anchored member of the immunoglobulin superfamily related to chicken contactin.

“…These include neural cell adhesion molecule (N-CAM) ~ (Barthels et al, 1987;Cunningham et al, 1987), myelinassociated glycoprotein (MAG) (Lai et al, 1987;Salzer et al, 1987), L1 (Moos et al, 1988), Po (Lemke et al, 1988), contactin (Ranscht, 1988)-which are expressed in vertebrates-and two recently identified insect proteins, fasciclin II (Harrelson and Goodman, 1988) and amalgam (Seeger et al, 1988). With the exception of Po, they contain C2-type Ig domains, and their sequence similarity extends in some cases beyond the Ig-like region (Harrelson and Goodman, 1988).…”

“…It has been proposed (Lai et al, 1987;Harrelson and Goodman, 1988) that a common, phylogenetically ancient role of C2-type domains may be to mediate cell adhesion or recognition phenomena during nervous system development. Another common trait shared by N-CAM, LI, and MAG is the presence of the L2/HNK-1 carbohydrate determinant .…”