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Developmental expression of proteolipid protein and DM20 mRNAs and proteins in the rat brain
S M LeVine1, D Wong, W B Macklin
1Department of Psychiatry, University of California, Los Angeles Medical Center.
Abstract:
Proteolipid protein (PLP) and DM20, two abundant proteins of myelin, are produced from alternatively spliced mRNAs from the primary PLP gene transcript. Recent studies on the mouse, bovine and human central nervous systems have found that DM20 protein is expressed prior to PLP during development. As development proceeds, however, PLP becomes the predominant protein. This implies that there must be some form of regulation controlling the ratio of these proteins during development. If this regulation occurs during transcription or splicing, the PLP/DM20 mRNA ratio should mimic the PLP/DM20 protein ratio during development. In order to study these closely related mRNAs, we developed a method that used oligonucleotide probes to specifically identify PLP or DM20 mRNA. In this study, we established that (1) as with other species studied, the DM20 protein is present at higher or equivalent levels to PLP during early rat brain development, and (2) PLP and DM20 mRNAs have essentially identical developmental profiles in the rat, although the DM20 mRNA is expressed at lower levels than PLP mRNA. Since the PLP/DM20 protein ratio in young rats does not reflect the PLP/DM20 mRNA ratio, the mechanism of regulation responsible for altering the PLP/DM20 protein ratio during development must occur after transcription and splicing. Possible posttranscriptional mechanisms controlling the ratio of these proteins during development are discussed.
Insights
Regulation of myelin protein ratios occurs post-transcriptionally. While proteolipid protein (PLP) and DM20 mRNA levels are similar during development, protein levels change, indicating post-transcriptional control of myelin composition.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Proteolipid protein (PLP) and DM20 are key myelin proteins.
- DM20 protein expression precedes PLP during development in various species.
- A shift in the PLP/DM20 protein ratio occurs during CNS development.
Purpose of the Study:
- To investigate the developmental regulation of PLP and DM20 mRNA and protein in the rat central nervous system.
- To determine if transcriptional or splicing events control the PLP/DM20 ratio.
- To identify the stage at which regulation occurs.
Main Methods:
- Developed a method using specific oligonucleotide probes to quantify PLP and DM20 mRNA.
- Analyzed protein and mRNA expression profiles during rat brain development.
- Compared developmental profiles of PLP/DM20 mRNA ratio with PLP/DM20 protein ratio.
Main Results:
- DM20 protein is present at higher or equivalent levels to PLP during early rat brain development.
- PLP and DM20 mRNAs exhibit nearly identical developmental profiles in rats.
- DM20 mRNA levels are lower than PLP mRNA levels throughout development.
Conclusions:
- The PLP/DM20 protein ratio changes during development in rats, but the mRNA ratio does not.
- Regulation of the PLP/DM20 protein ratio occurs after transcription and splicing.
- Post-transcriptional mechanisms are likely responsible for modulating myelin protein composition during development.