Molecular Neurobiology

, Volume 2, Issue 1, pp 41–89 | Cite as

Cellular and molecular aspects of myelin protein gene expression

  • Anthony T. Campagnoni
  • Wendy B. Macklin


The cellular and molecular aspects of myelin protein metabolism have recently been among the most intensively studied in neurobiology. Myelination is a developmentally regulated processinvolving the coordination of expression of genes encoding both myelin proteins and the enzymes involved in myelin lipid metabolism. In the central nervous system, the oligodendrocyte plasma membrane elaborates prodigious amounts of myelin over a relatively short developmental period. During development, myelin undergoes characteristic biochemical changes, presumably correlated with the morphological changes during its maturation from loosely-whorled bilayers to the thick multilamellar structure typical of the adult membrane.

Genes encoding four myelin proteins have been isolated, and each of these specifies families of polypeptide isoforms synthesized from mRNAs derived through alternative splicing of the primary gene transcripts. In most cases, the production of the alternatively spliced transcripts is developmentally regulated, leading to the observed protein compositional changes in myelin. The chromosomal localizations of several of the myelin protein genes have been mapped in mice and humans, and abnormalities in two separate genes appear to be the genetic defects in the murine dysmyelinating mutants,shiverer andjimpy. Insertion of a normal myelin basic protein gene into theshiverer genome appears to correct many of the clinical and cell biological abnormalities associated with the defect. Most of the dysmyelinating mutants, including those in which the genetic defect is established, appear to exhibit pleiotropy with respect to the expression of other myelin genes.

Post-translational events also appear to be important in myelin assembly and metabolism. The major myelin proteins are synthesized at different subcellular locations and follow different routes of assembly into the membrane. Prevention of certain post-translational modifications of some myelin proteins can result in the disruption of myelin structure, reminiscent of naturally occurring myelin disorders. Studies on the expression of myelin genes in tissue culture have shown the importance of epigenetic factors (e. g., hormones, growth factors, and cell-cell interactions) in modulating myelin protein gene expression. Thus, myelinogenesis has proven to be very useful system in which to examine cellular and molecular mechanisms regulating the activity of a nervous system-specific process.

Index Entries

Myelin protein gene expression post-transitional events isoforms in whole brain, developmental changes 



Base pair(s)


Complementary DNA


2′,3′-cyclic nucleotide 3′-phosphodiesterase


Central nervous system


25 kdalton myelin proteolipid protein


Galactosyl Ceramide




Myelin associated glycoprotein


Myelin basic protein




Polyacrylamide gel electrophoresis


(30 kdalton myelin) proteolipid protein


Peripheral nervous system




Subacute combined degeneration


Sodium dodecyl sulfate




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Copyright information

© Humana Press Inc. 1988

Authors and Affiliations

  • Anthony T. Campagnoni
    • 1
  • Wendy B. Macklin
    • 1
  1. 1.Mental Retardation Research CenterUCLA Center for the Health SciencesLos Angeles

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