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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
Article

Abstract

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 

Nomenclature

bp

Base pair(s)

cDNA

Complementary DNA

CNP

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

CNS

Central nervous system

DM20

25 kdalton myelin proteolipid protein

GC

Galactosyl Ceramide

GM4

Sialosylgalactosylceramide

MAG

Myelin associated glycoprotein

MBP

Myelin basic protein

nt

Nucleotide(s)

PAGE

Polyacrylamide gel electrophoresis

PLP

(30 kdalton myelin) proteolipid protein

PNS

Peripheral nervous system

RIA

Radioimmunoassay

SCD

Subacute combined degeneration

SDS

Sodium dodecyl sulfate

T3

Triiodothyronine

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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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