Article ; Online: Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination.
2024 Volume 10, Issue 15, Page(s) eadm7600
Abstract: Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are ... ...
| Abstract | Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a notable absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves. Our data indicate that neddylation exerts a global influence on the complex transcriptional and posttranscriptional program by simultaneously regulating the expression and function of multiple essential myelination signals, including the master transcription factor EGR2 and the negative regulators c-Jun and Sox2, and inducing global secondary changes in downstream pathways, including the mTOR and YAP/TAZ signaling pathways. This places neddylation as a critical regulator of myelination and delineates the potential pathogenic mechanisms involved in CMT mutations related to neddylation. |
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| MeSH term(s) | Animals ; Mice ; Schwann Cells ; Myelin Sheath/genetics ; Charcot-Marie-Tooth Disease/genetics ; Mutation ; Protein Processing, Post-Translational |
| Language | English |
| Publishing date | 2024-04-12 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2810933-8 |
| ISSN | 2375-2548 ; 2375-2548 |
| ISSN (online) | 2375-2548 |
| ISSN | 2375-2548 |
| DOI | 10.1126/sciadv.adm7600 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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