Differential splicing of MAG transcripts during CNS and PNS development

doi:10.1016/0169-328X(88)90006-X

Molecular Brain Research

Volume 4, Issue 2, September 1988, Pages 143-155

https://doi.org/10.1016/0169-328X(88)90006-X Get rights and content

Abstract

Myelin-associated glycoprotein (MAG) is expressed on the surface of glial cells and is thought to act as a glial-neuronal adhesion molecule during early stages in the myelination process. Sequencing of several cDNA clones predicted the existence of two classes of MAG mRNAs which differ in the presence or absence of a 45 nucleotide insert near the 3′ end. These two mRNAs are sufficient to encode the two MAG proteins previously described (p67MAG and p72MAG) and show that they differ only in their carboxyl terminal regions. The results of RNAse protection experiments reported here confirm the existence of two mRNAs for MAG which arise by alternative splicing of exon 12, as shown by Lai et al.²¹. Our results show that the p72MAG mRNA is expressed during the time of active myelin formation in the CNS, reaching a peak by post-natal day 22 and thereafter declining to adult levels by day 62. Conversely, p67MAG mRNA is produced as the minor species during myelin formation, but becomes the predominant form in adult brain. Cultures of oligodendrocytes express both forms of MAG. In the PNS, mRNA coding for p67MAG is predominant throughout development, reaching peak levels at day 6–10, whereas p72MAG mRNA is a very minor species. Alternative splciing also occurs at the 5′ terminus. One form of mRNA lacking exon 2 from the 5′ non-coding region is predominant in PNS, whereas mRNA containing exon 2 predominates in the CNS. Therefore, at least two and possibly four different mRNA species encode MAG. These results confirm the hypothesis that the two forms of MAG (p67 and p72) are generated by alternative splicing and show that each form is differentially regulated during development in the CNS and PNS.

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Citation Excerpt :
In the nervous system MAG exists predominantly as two isoforms identified as S-MAG (short) and L-MAG (long) that arise from an alternative splicing that produces two proteins with identical extracellular and transmembrane domains but that differ in the length of their cytosolic tails [41–43]; while the difference in their cytosolic domains is traduced in unique signaling capacities [32,44–48]. MAG expression is regulated temporally and spatially in the nervous system; with L-MAG predominating during CNS development and during myelination whereas S-MAG accumulates at later stages [49–51]. Similarly, both isoforms of MAG are expressed in rat OLs cultures [52].
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Research reportDifferential splicing of MAG transcripts during CNS and PNS development

Abstract

Brain Res.

Anal. Biochem.

Neuroscience

Cell

Gene

Cell

Cell

Molecular cloning and primary structure of myelin associated glycoprotein

Protein determinants of myelination in different regions of developing rat central nervous system

Biochem. J.

Isolation and nucleotide sequence of mouse NCAM cDNA that codes for a Mr 79000 polypeptide without a membrane spanning region

EMBO J.

Differentiated rat glial cell strain is tissue culture

Science

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

Biochemistry

Immunochemical measurement of myelin basic protein in developing rat brain: an index of myelin synthesis

Dev. Biol.

Emergence of three myelin proteins in oligodendrocyte cultured without neurons

J. Cell Biol.

Myelin associated glycoprotein, a cell adhesion molecule of oligodendrocytes, is phospharylated in brain

Mol. Cell. Biol.

Two developmentally regulated messenger RNAs differing in their coding region may exist for the myelin associated glycoprotein

J. Biol. Chem.

Developmental expression of the myelin associated glycoprotein in the peripheral nervous system is different from that in the central nervous system

J. Neurochem.

The Myelin Associated Glycoprotein in Development and Disease

Myelin formation in the sciatic nerve of the rat: a quantitative electron microscopic, histochemical and autoradiographic study

J. Neuropathol. Exp. Neurol.

A subcloning strategy for DNA sequences

Nucl. Acid Res.

Sequence of a cDNA clone encoding the polysialic acid rich and cytoplasmic domains of the neural cell adhesion molecule (N-CAM)

Sequence of myelinization in the brain of the albino rat. A. Cerebral cortex, thalamus and related structures

J. Comp. Neurol.

Two forms of the 1B236 myelin associated glycoprotein, a cell adhesion molecule for postnatal neural development are produced by alternative splicing

Research report
Differential splicing of MAG transcripts during CNS and PNS development