Interactive Repression of MYRF Self-Cleavage and Activity in Oligodendrocyte Differentiation by TMEM98 Protein

The Journal of Neuroscience, 2018 · DOI: https://doi.org/10.1523/JNEUROSCI.0154-18.2018 · Published: November 14, 2018

Simple Explanation

Oligodendrocytes (OLs) form myelin sheaths essential for fast nerve signal transmission. MYRF is a key protein that controls OL development and myelin maintenance. MYRF needs to be cut into two pieces to work. This study finds that TMEM98 protein can bind to MYRF and prevent this cutting, thus inhibiting MYRF's function. This TMEM98 protein is found in early developing OLs, suggesting it acts as a check, preventing MYRF from activating myelin gene expression too early.

Study Duration

Not specified

Participants

Mouse pups and embryonic chicken of either sex

Evidence Level

Not specified

Key Findings

1
TMEM98 binds to the C-terminal of MYRF, preventing its self-cleavage.
2
TMEM98 inhibits the translocation of the N-fragment of MYRF into the nucleus, which is necessary for gene activation.
3
Forced expression of TMEM98 suppresses oligodendrocyte differentiation and MYRF-induced myelin gene expression in embryonic chicken spinal cord.

Research Summary

This study identifies TMEM98 as a MYRF-interacting protein that inhibits MYRF self-cleavage and nuclear translocation, thereby negatively regulating oligodendrocyte differentiation. TMEM98 is selectively expressed in early maturing oligodendrocytes in the developing CNS, suggesting a role in regulating the timing of myelination. The findings provide new insights into the mechanisms regulating MYRF activity during oligodendrocyte differentiation and myelination, highlighting the importance of regulated proteolysis in this process.

Practical Implications

Understanding Myelination

Provides a deeper understanding of the molecular mechanisms controlling oligodendrocyte differentiation and myelination.

Therapeutic Targets

Identifies TMEM98 as a potential therapeutic target for manipulating myelination in demyelinating diseases.

Regulated Proteolysis

Highlights the importance of regulated proteolysis of membrane-bound transcription factors in development.

Study Limitations

1
The precise molecular mechanism by which TMEM98 inhibits MYRF cleavage remains unknown.
2
The study primarily focuses on in vitro and in ovo experiments, further in vivo studies are needed to confirm the findings.
3
The role of the C-terminal fragment of MYRF in OL differentiation is not fully elucidated.

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